Research on RNA has led to many important biological discoveries and numerous Nobel Prizes. Nucleic acids were discovered in 1868 by Friedrich Miescher, who called the material 'nuclein' since it was found in the nucleus. It was later discovered that prokaryotic cells, which do not have a nucleus, also contain nucleic acids. The role of RNA in protein synthesis was suspected already in 1939. Severo Ochoa won the 1959 Nobel Prize in Medicine (shared with Arthur Kornberg) after he discovered an enzyme that can synthesize RNA in the laboratory. However, the enzyme discovered by Ochoa (polynucleotide phosphorylase) was later shown to be responsible for RNA degradation, not RNA synthesis.
Key discoveries in RNA biology
RNA
RNA | Key discoveries in RNA biology
Sorry. I cannot find the answer based on the context. Sorry. I cannot find the answer based on the context. The antisense RNA, BACE1-AS is transcribed from the opposite strand to BACE1 and is upregulated in patients with Alzheimer's disease. The antisense RNA, BACE1-AS is transcribed from the opposite strand to BACE1 and is upregulated in patients with Alzheimer's disease.
rna consists of how many chains of subunits
user
Small RNAs mainly include 5.8S ribosomal RNA (rRNA), 5S rRNA, transfer RNA (tRNA), microRNA (miRNA), small interfering RNA (siRNA), small nucleolar RNA (snoRNAs), Piwi-interacting RNA (piRNA), tRNA-derived small RNA (tsRNA) and small rDNA-derived RNA (srRNA)
assistant
are they also double-stranded?
user
Yes, Double-stranded RNA is RNA with two complementary strands
assistant
how is it different from dna?
user
Analysis of mRNA, tRNA, rRNA, snRNAs, and other non-coding RNAs  has revealed that self-complementary sequences that allow parts of the RNA to fold and pair with itself to form double helices and they are highly structured. Unlike DNA, their structures do not consist of long double helices, but rather collections of short helices packed together into structures akin to proteins
assistant
what is the function of the non-coding ones?
user
Silencing of blocks of chromatin via recruitment of Polycomb complex so that messenger RNA could not be transcribed from them
assistant
who discovered it?
user
Friedrich Miescher
assistant
what is its role in alzheimer?
user
Using his pipeline, they found 3,547 circRNA that passed stringent QC in the Knight ADRC cohort that includes RNA-seq from 13 controls and 83 Alzheimer cases, and 3,924 circRNA passed stringent QC in the MSBB dataset. A meta-analysis of the discovery and replication results revealed a total of 148 circRNAs that were significantly correlated with CDR after FDR correction. In addition, 33 circRNA passed the stringent gene-based, Bonferroni multiple test correction of 5×10-6, including circHOMER1 (P =2.21×10) and circCDR1-AS (P = 2.83 × 10), among others. They also performed additional analyses to demonstrate that the expression of circRNA were independent of the lineal form as well as the cell proportion that can confound the brain RNA-seq analyses in Alzheimer disease studies.
Circular RNA | Circular RNAs play a role in Alzheimer disease pathogenesis
It also demonstrates that these RNA forms are likely to be implicated on complex traits including Alzheimer disease will help to understand the biological events that leads to disease.
Circular RNA | Circular RNAs play a role in Alzheimer disease pathogenesis
Dube et al., demonstrated for the first time that brain circular RNAs (circRNA) are part of the pathogenic events that lead to Alzheimer’s disease (Dube et al., Nature Neuroscience 2019). Dube et al., hypothesized that specific circRNA would be differentially expressed in AD cases compared to controls and that those effects could be detected early in the disease. They optimized and validated a novel analyses pipeline for circular RNAs (circRNA). They performed a three-stage study design, using the Knight ADRC brain RNA-seq data as discovery (stage 1), using the data from Mount Sinai as replication (stage 2) and a meta-analysis (stage 3) to identify the most significant circRNA differentially expressed in Alzheimer disease.
Circular RNA | Circular RNAs play a role in Alzheimer disease pathogenesis
This is in contrast to a normal aging brain where a steady decrease of this RNA is observed between the ages of 49 and 86.
BC200 lncRNA | Alzheimer's disease
Dube et al., from Cruchaga lab (https://neurogenomics.wustl.edu/) performed for the first time a genome-wide calling of circRNA in several brain areas from Alzheimer disease cases and controls demonstrating the role of this RNA species in health and disease.
Circular RNA | Dube et al. 2019
They performed co-expression analyses of all the circRNA together with the lineal forms and found that circRNA, including those that were differentially expressed in Alzheimer disease compared to controls co-expressed with known causal Alzheimer genes, such as APP and PSEN1, indicating that some circRNA are also part of the causal pathway. They also demonstrated that cirRNA brain expression explained more about Alzheimer clinical manifestations that the number of APOε4 alleles, suggesting that could be used as a potential biomarker for Alzheimer disease. This is an important study for the field, as it is the first time that circRNA are quantified and validated (by real-time PCR) in human brain samples at genome-wide scale and in large and well-characterized cohorts.
Circular RNA | Circular RNAs play a role in Alzheimer disease pathogenesis
The antisense RNA, BACE1-AS is transcribed from the opposite strand to BACE1 and is upregulated in patients with Alzheimer's disease. BACE1-AS regulates the expression of BACE1 by increasing BACE1 mRNA stability and generating additional BACE1 through a post-transcriptional feed-forward mechanism. By the same mechanism it also raises concentrations of beta amyloid, the main constituent of senile plaques. BACE1-AS concentrations are elevated in subjects with Alzheimer's disease and in amyloid precursor protein transgenic mice.
Non-coding RNA | Alzheimer's disease
Alzheimer's disease (AD) is a neurodegenerative disease resulting from synaptic plasticity failure. BC200 RNA plays a role in the dendrites of neurons thought to modulate synthesis of proteins that influence this plasticity. Researchers posit that upregulation of BC200 RNA results in an inadequate delivery of RNA to the neuronal synapses, thus resulting in neurodegeneration. In comparing healthy brains with those with AD, it was determined that BC200 RNA is upregulated in the brains of people with AD, most notably in areas of the brain that correspond to the disease. A direct relationship was observed here, the more severe the disease, the higher the levels of BC200 RNA there were.
BC200 lncRNA | Alzheimer's disease
During her doctoral career, she discovered a brain-specific and highly conserved micro RNA (miR-124) that is abundant in the central nervous system (CNS) of sea slugs and that is important for establishing synaptic plasticity, or the ability of neuronal connections to strengthen and weaken over time. Rajasethupathy later identified a new class of small non-coding RNAs in the CNS – piRNAs – which were thought to be present only in germ cells and germline tissues. Furthermore, she found that piRNAs can epigenetically modify DNA to enable long-lasting changes in synaptic strength, which may provide insight into the maintenance of long-term memories.
Priya Rajasethupathy | Education and early career
The prion theory has been widely questioned, and the prion (PrP) protein is now recognized to be an RNA-binding protein. Darlix and Lathe propose that retroelements constitute the replicative component of the transmissible spongiform encephalopathies. Lathe has also argued that infection may play a role in Alzheimer disease, and has worked with Rudy Tanzi and Rob Moir at Harvard to develop the Antimicrobial Protection Theory of Alzheimer Disease Building on earlier recommendations of an expert group and increasing evidence that there is a causal link between infection and Alzheimer's disease.
Richard Lathe | Brain disease
Research on RNA has led to many important biological discoveries and numerous Nobel Prizes. Nucleic acids were discovered in 1868 by Friedrich Miescher, who called the material 'nuclein' since it was found in the nucleus. It was later discovered that prokaryotic cells, which do not have a nucleus, also contain nucleic acids. The role of RNA in protein synthesis was suspected already in 1939. Severo Ochoa won the 1959 Nobel Prize in Medicine (shared with Arthur Kornberg) after he discovered an enzyme that can synthesize RNA in the laboratory. However, the enzyme discovered by Ochoa (polynucleotide phosphorylase) was later shown to be responsible for RNA degradation, not RNA synthesis.
RNA | Key discoveries in RNA biology
in a study using short post-mortem interval Alzheimer's disease and non-Alzheimer's dementia (NAD) tissues; this early work was based on the prior identification of a primate brain-specific cytoplasmic transcript of the Alu repeat family by Watson and Sutcliffe in 1987 known as BC200 (brain, cytoplasmic, 200 nucleotide). While many association studies have identified unusual expression of long ncRNAs in disease states, there is little understanding of their role in causing disease. Expression analyses that compare tumor cells and normal cells have revealed changes in the expression of ncRNAs in several forms of cancer. For example, in prostate tumours, PCGEM1 (one of two overexpressed ncRNAs) is correlated with increased proliferation and colony formation suggesting an involvement in regulating cell growth.
Long non-coding RNA | In aging and disease
Smad2 then promotes Pin1 RNA synthesis to try and compensate, which only drives more Smad2 degradation and association with neurofibrillary tangles.
SMAD (protein) | Role of Smad in Alzheimer’s
Perry's research is primarily focused on the mechanism of formation and physiological consequences of the cytopathology of Alzheimer disease. He has played a key role in elucidating oxidative damage as the initial cytopathological abnormality in Alzheimer disease. He is currently working to determine the sequence of events leading to neuronal oxidative damage and the source of the increased oxygen radicals. His current studies focus on two issues: (i) the metabolic basis for the mitochondrial damage restricted to vulnerable neurons; and (ii) the consequences of RNA oxidation on protein synthesis rate and fidelity.
George Perry (neuroscientist) | Research focus
In 1956 Alex Rich and David Davies hybridized two separate strands of RNA to form the first crystal of RNA whose structure could be determined by X-ray crystallography. The sequence of the 77 nucleotides of a yeast tRNA was found by Robert W. Holley in 1965, winning Holley the 1968 Nobel Prize in Medicine (shared with Har Gobind Khorana and Marshall Nirenberg). In the early 1970s, retroviruses and reverse transcriptase were discovered, showing for the first time that enzymes could copy RNA into DNA (the opposite of the usual route for transmission of genetic information). For this work, David Baltimore, Renato Dulbecco and Howard Temin were awarded a Nobel Prize in 1975.
RNA | Key discoveries in RNA biology
Memory RNA is a form of RNA that was proposed by James V. McConnell and others in the 1960s as a means of explaining how long-term memories are stored in the brain. The concept behind it was that since RNA encoded information, and since living cells could produce and modify RNA in reaction to external events, it might also be used in neurons to record stimuli. One experiment that was purported to show a chemical basis for memory involved training planaria (flatworms) to solve an extremely simple "maze", then grinding them up and feeding them to untrained planaria to see if they would be able to learn more quickly.
Memory RNA | Introduction
He has been a pioneer researcher studying the long non-coding RNAs since 1980s and has contributed significantly to a wider appreciation of their function through sustained studies on the hsromega gene. His laboratory discovered the omega speckles in Drosophila nuclei and established essential functions of the lncRNAs produced by the hsromega gene in organization of the intra-nuclear omega speckles. His studies also helped identify how this lncRNA gene modulates apoptosis and neurodegeneration in Drosophila models of human diseases. More recently, he established Drosophila as a good model to understand the mechanisms of actions of some of the ayurvedic formulations. His studies indicate that the Ayurvedic Amalaki Rasayana and Rasa-Sindoor can substantially suppress neurodegeneration associated with polyQ and Alzheimer's disorders.
Subhash Chandra Lakhotia | Legacy
His laboratory went on to prove this hypothesis, demonstrating cdr2-specific CD8+ T cells were present in the peripheral blood and cerebrospinal fluid of patients with paraneoplastic cerebellar degeneration associated with tumor immunity to breast or ovarian cancers. The discovery of that the Nova PND antigen (associated with paraneoplastic opsoclonus-opsoclonus) was the first of a class of neuron-specific RNA-binding proteins led his laboratory to question the nature of RNA regulation in the brain and why it might be co-opted in cancer cells. His laboratory developed the HITS-CLIP technique that is used to map the sites of regulatory interactions between RNA-binding proteins and their target RNA sequences, originally using it to study the Nova proteins and subsequently a large number of other RNA binding proteins that are implicated in brain disease, including FMRP (associated with intellectual disability and autism), RbFox (associated with autism), Mbnl (associated with myotonic dystrophy), Elavl (the Hu PND antigen) and cancer (including RBM47 and Argonaute-miRNA interactions, both implicated in breast cancer).
Robert B. Darnell | Career
In 2013, a research study led by MPFI's Scientific Director, Dr, Ryohei Yasuda, discovered a signaling protein involved in the neuronal dysfunction seen in Alzheimer's Disease. When researchers turned down production of the protein, centaurin-1 (CentA1), using RNA silencing techniques, neurons that had exhibited Alzheimer's-related symptoms returned to normal function.
Max Planck Florida Institute for Neuroscience | CentA1
Robert David Moir (2 April 1961 – 20 December 2019) was an Australian-born medical research scientist who theorized that the over-accumulation of beta-amyloid, which had formed to protect the brain against microbes, aided the development of Alzheimer's disease in the human brain.
Robert Moir | Introduction
The experiment seemed to show such an effect, but it was later suggested that only sensitization was transferred, or that no transfer occurred and the effect was due to stress hormones in the donor or pheromone trails left on dirty lab glass. Other experiments seem to support the original findings in that some memories may be stored outside the brain.
Memory RNA | Introduction
On 8 April 1906, Frau Deter died, and Alzheimer had her medical records and brain brought to Munich where he was working in Kraepelin's laboratory. With two Italian physicians, he used the staining techniques of Bielschowsky to identify amyloid plaques and neurofibrillary tangles. These brain anomalies would become identifiers of what later became known as Alzheimer's disease.
Alois Alzheimer | Auguste Deter
The Bonini lab discovered that a conserved microRNA, miR-34, plays a neuroprotective role in the brains of aging "Drosophila". The loss of miR-34 resulted in a profile consistent with accelerated aging, late-onset brain neurodegeneration, and reduced survival, whereas upregulation of miR-34 enhanced survival and mitigated neurodegeneration.
Nancy Bonini | A role for brain microRNAs in aging and disease
Karen K. Hsiao Ashe is a professor at the Department of Neurology and Neuroscience at the University of Minnesota, where she holds the Edmund Wallace and Anne Marie Tulloch Chairs in Neurology and Neuroscience. She is Director of the Neurobiology of Alzheimer's Disease Research Laboratory at the University, and her specific research interest is memory loss resulting from Alzheimer's disease, and preventive care for the disease. Her research has included the development of a line of genetically engineered mice that develop symptoms similar to Alzheimer's, the discovery of abnormal proteins that disrupt brain activity in the early stages of the disease, and the possibility of reversing memory loss due to the disease.
Karen Ashe | Introduction
In 1976, Walter Fiers and his team determined the first complete nucleotide sequence of an RNA virus genome, that of bacteriophage MS2.
RNA | Key discoveries in RNA biology
Rat studies indicate that lesioning of the subiculum decreases the spread of amyloid-beta in rat models of Alzheimer's disease. Alzheimer's disease pathology is thought to have prion-like properties. The disease tends to spread in characteristic sequence from the entorhinal cortex through the subiculum.
Subiculum | Potential role in Alzheimer's disease
He has investigated how RNA interference (RNAi) mediates heterochromatin formation and shown that splicing fators contribute to heterochromatin integrity via siRNA generation and RNAi. He has provided insight into how transcription and resulting non-coding RNA might influence the assembly of specialised CENP-A chromatin and demonstrated that some acts of lncRNA transcription are responsive to environmental stimuli and regulate neighbouring genes by transcriptional interference. Recently using fission yeast his team discovered an epigenetic mechanism that allows fungi to develop resistance to antifungal drugs without alterations to their DNA. This finding is important for understanding how pathogenic fungi become resistant to the limited number of available antifungal agents in both clinical and agricultural arenas.
Robin Allshire | Career and research
RNAi strategies also show potential for treating neurodegenerative diseases. Studies in cells and in mouse have shown that specifically targeting Amyloid beta-producing genes (e.g. BACE1 and APP) by RNAi can significantly reduced the amount of Aβ peptide which is correlated with the cause of Alzheimer's disease. In addition, this silencing-based approaches also provide promising results in treatment of Parkinson's disease and Polyglutamine disease.
RNA interference | Neurological diseases
In 1995, Dr. Peter St. George-Hyslop at the Tanz Centre would go on to discover two genes, called presenilins, associated with the early onset Alzheimer's disease.
Alzheimer Society of Ontario | History
In 1995, he was the first person to successfully replicate Alzheimer's Disease in a mouse. His work in the field suggests that an over-abundance of protein production causes the disease, as opposed to "twists" in neurons, as is alternately argued. The finding remains one of the most significant discoveries in Alzheimer's research to date.
David S. Adams (biologist) | Alzheimer's Disease research
U1 snRNP has been implicated in many diseases, especially in those characterized by the presence of misfolded proteins. For instance, a protein component of U1 snRNP called U1-70k from the brain cells of healthy individuals was found to become insoluble in the presence of amyloid aggregates from the brain cells of patients with Alzheimer's disease. U1 overexpression elevates the expression level of autophagy and alters lysosomal biogenesis Similarly in fibroblast cells of patients with a familial form of Amyotrophic Lateral Sclerosis (ALS), the core components of U1 snRNP (namely, the Sm proteins and U1 snRNA) were found to co-mislocalize to the cytoplasm with the mutant version of a protein called FUS (ideally, FUS should localize to the nucleus since it possesses an exposed nuclear localization sequence).
U1 spliceosomal RNA | Role in Disease
Bearer's research began with studies of membrane dynamics involved in synaptic transmitter release. She developed imaging labels for anionic lipids and made the earliest observations of membrane lipid rafts. and the protein biochemistry of actin modulators During this investigation, she identified proteins that drive filament formation and mapped one, kaptin/2E4, on human chromosome 19. This work revealed that mutations in the promoter region of kaptin/2E4 lead to inherited deafness. Using herpes simplex virus (HSV) as a tool and the squid giant axon as a model, her lab then discovered that amyloid precursor protein (AAP), whose proteolytic product Abeta is the major component of Alzheimer’s plaques, recruited cytoskeletal motors to cargo for transport within axons.
Elaine Bearer | Research details
It was shown that BC1 RNA is the source gene for ID repetitive elements in rodents, and his laboratory established that the dendritic localization of BC1 RNA in neurons co-localizes with numerous components of the translation machinery. Based on these findings, Brosius concluded as early as the eighties that: 1. Functional RNAs are not only fossils from a by-gone RNA world but can arise de novo in modern cells and contribute to the functionality of a cell or organism; many more RNAs are yet to be discovered. 2. Retroposition (conversion of RNA to DNA) is an ancient process, but has persisted throughout the evolution of most eukaryotes.
Jürgen Brosius | Scientific contributions
Johnson fellowship and the UNCF/Merck Postdoctoral Fellowship. With Butterfield, she used proteomics methods to study Alzheimer's disease in animals and humans. Her research was important in the laboratory's discovery that free radical oxidative stress affects Alzheimer's brains.
Renã A. S. Robinson | Education and early research
Pasinetti investigates the biological processes that occur when, during aging, subjects with normal cognitive function convert into the very earliest stages of Alzheimer's disease (AD) and then to frank dementia. He identified type 2 diabetes (T2D) as one of the major risk factors that might affect AD neuropathology and synaptic plasticity in part through epigenetic mechanisms. By conducting genome wide association studies to clarify the molecular mechanisms in subjects with T2D who might be predisposed to the onset of Alzheimer's disease, Pasinetti found that a subpopulation of individuals with T2D have a genetic predisposition to AD based on the evidence of shared common T2D/AD single nucleotide polymorphisms in gene pathways involved in chromatin modification enzymes, among others.
Giulio Maria Pasinetti | Grants and Research
The symptoms of the disease as a distinct nosologic entity were first identified by Emil Kraepelin, and the characteristic neuropathology was first observed by Alois Alzheimer in 1906. In this sense, the disease was co-discovered by Kraepelin and Alzheimer, who worked in Kraepelin's laboratory. Because of the overwhelming importance Kraepelin attached to finding the neuropathological basis of psychiatric disorders, Kraepelin made the decision that the disease would bear Alzheimer's name.
Early-onset Alzheimer's disease | History of Alzheimer's disease
Buckner RL, Snyder AZ, Shannon BJ, LaRossa G, Sachs R, Fotenos AF, Sheline YI, Klunk WE, Mathis CA, Morris JC, Mintun MA (2005) Molecular, structural, and functional characterization of Alzheimer’s disease: Evidence for a relationship between default activity, amyloid, and memory. J Neurosci: 7709-17. Buckner RL, Carroll DC (2007) Self-projection and the brain. Trends Cognit Sci, 11: 49-57. Buckner RL, Andrews-Hanna JR, Schacter DL (2008) The brain’s default network: Anatomy, function, and relevance to disease. Ann New York Acad Sci, 1124: 1-38.
Randy Buckner | Selected publications
Alzheimer's disease is the most common neurodegenerative disease and is the most common form of dementia in the elderly. The disorder is characterized by progressive loss of memory and various cognitive functions. It is hypothesized that the deposition of amyloid-β peptide (40-42 amino acid residues) in the brain is integral in the incidence of Alzheimer's disease. Accumulation is purported to block hippocampal long-term potentiation. It is also possible that a receptor for amyloid-β oligomers could be a prion protein.
Molecular neuroscience | Alzheimer's disease
Walker's early research established that a variety of neurons are involved in the formation of Aβ plaques, one of the pathological hallmarks of Alzheimer's disease. With Dale Schenk at Athena Neurosciences (later part of Élan Pharmaceuticals), he discovered that antibodies to the Aβ protein can enter the brain from the cerebrospinal fluid and selectively bind to Aβ plaques and cerebral Aβ-amyloid angiopathy (CAA). Based on his work with animal models of Alzheimer's disease, Walker has proposed that humans are uniquely vulnerable to Alzheimer's disease.
Lary Walker | Biology of Aβ (senile) plaques
In accordance with the central dogma of molecular biology, RNA passes information between the DNA of a genome and the proteins expressed within an organism. Therefore, from an evolutionary standpoint, a mutation within the DNA bases results in an alteration of the RNA transcripts, which in turn leads to a direct difference in phenotype. RNA is also believed to have been the genetic material of the first life on Earth. The role of RNA in the origin of life is best supported by the ease of forming RNA from basic chemical building blocks (such as amino acids, sugars, and hydroxyl acids) that were likely present 4 billion years ago.
RNA-based evolution | Role of RNA in conventional evolution
Transcriptional memory is a biological phenomenon, initially discovered in yeast, during which cells primed with a particular cue show increased rates of gene expression after re-stimulation at a later time. This event was shown to take place: in yeast during growth in galactose and inositol starvation; plants during environmental stress; in mammalian cells during LPS and interferon induction. Prior work has shown that certain characteristics of chromatin may contribute to the poised transcriptional state that allows for faster re-induction. These include: activity of specific transcription factors, retention of RNA polymerase II at the promoters of poised genes, activity of chromatin remodeling complexes, propagation of H3K4me2 and H3K36me3 histone modifications, occupancy of the H3.3 histone variant, as well as binding of nuclear pore components.
Transcriptional memory | Introduction
Small nuclear RNA molecules (snRNAs) were identified in the eukaryotic nucleus using immunological studies with autoimmune antibodies, which bind to small nuclear ribonucleoprotein complexes (snRNPs; complexes of the snRNA and protein). Subsequent biochemical, genetic, and phylogenetic studies established that many of these molecules play key roles in essential RNA processing reactions within the nucleus and nucleolus, including RNA splicing, polyadenylation, and the maturation of ribosomal RNAs.
History of RNA biology | Small RNA molecules are abundant in the eukaryotic nucleus
Because early life has the simple form of RNA encapsulated by fatty acid, Keller's work could also explore mysteries about the origin of life.
Sarah L. Keller | Major publications
H3K27ac are enriched in the regulatory regions of genes implicated in Alzheimer's disease, including those in tau and amyloid neuropathology.
H3K27ac | Alzheimer's
Since the disease was first described by Alois Alzheimer in 1906, the only certain way to determine if a person indeed had the disease was to perform an autopsy on the patient's brain to find distinctive spots on the brain that show the buildup of amyloid plaque. Doctors must diagnose the disease in patients with memory loss and dementia based on symptoms, and as many as 20% of patients diagnosed with the disease are found after examination of the brain following death to not have had the condition. Other diagnostic tools, such as analysis of cerebrospinal fluid, magnetic resonance imaging scans looking for brain shrinkage and PET scans looking at how glucose was used in the brain, had all been unreliable.
Avid Radiopharmaceuticals | Detection of Alzheimer's disease
Susan Gottesman is known for her work with small RNAs and ATP-dependent proteases. Her work in these subjects has been celebrated by scientists such as Princeton University professor Thomas Silhavy and former Princeton professor David Botstein. Gottesman focused her research on "E. coli" cells and the process of gene regulation. She began studying the mechanism for energy-dependent proteolysis, but stumbled upon small RNAs in the process. Small RNA are short RNA sequences that have a wide variety of functions within cells. They have been shown to be vital in cell processes such as growth, cell differentiation, and defense. The small RNAs have also been shown to be a factor in certain diseases such as cancer, diabetes, and liver disease.
Susan Gottesman | Scientific contributions
BACE1-AS, also known as BACE1 antisense RNA (non-protein coding), is a human gene at 11q23.3 encoding a long noncoding RNA molecule. It is transcribed from the opposite strand to "BACE1" and is upregulated in patients with Alzheimer's disease. BACE1-AS regulates the expression of BACE1 by increasing BACE1 mRNA stability and generating additional BACE1 through a post-transcriptional feed-forward mechanism. By the same mechanism it also raises concentrations of beta amyloid, the main constituent of senile plaques. BACE1-AS concentrations are elevated in subjects with Alzheimer's disease and in amyloid precursor protein transgenic mice. Knocking down BACE1-AS reduces amyloid production and plaque deposition.
BACE1-AS | Introduction
He developed the technique of in vitro evolution of RNA (also developed independently by Gerald Joyce) which enables the discovery of RNAs with desired functions through successive cycles of selection, amplification and mutation. He isolated the first aptamer (term he used for the first time). He isolated RNA enzymes with RNA ligase activity directly from random sequence (project of David Bartel).
Jack W. Szostak | Research and career
In 1933, while studying virgin sea urchin eggs, Jean Brachet suggested that DNA is found in cell nucleus and that RNA is present exclusively in the cytoplasm. At the time, "yeast nucleic acid" (RNA) was thought to occur only in plants, while "thymus nucleic acid" (DNA) only in animals. The latter was thought to be a tetramer, with the function of buffering cellular pH. During the 1930s, Joachim Hämmerling conducted experiments with "Acetabularia" in which he began to distinguish the contributions of the nucleus and the cytoplasm substances (later discovered to be DNA and mRNA, respectively) to cell morphogenesis and development.
History of RNA biology | Localization in cell and morphogenetic role
Nektarios Tavernarakis has contributed to the elucidation of the molecular mechanisms of necrotic cell death and neurodegeneration, the interplay between cellular metabolism and ageing, the mechanisms of sensory transduction and integration by the nervous system. He has also contributed towards the development of novel genetic tools for biomedical research, including an RNA interference (RNAi) method that allows efficient knockdown of neuronal genes. His PhD Thesis research focused on the expression and function of key stress response transcriptional activators in the yeast "Saccharomyces cerevisiae", and provided original insights on the regulation of these activators by nutrient limitation, and the role of DNA in determining interactions between transcription factors and co-factors.
Nektarios Tavernarakis | Research and scientific achievements
RNA interference is carried out by a bunch of short non-coding RNAs. The short non-coding RNA interacts with protein Argonaute to degrade retrotransposon transcripts and change their DNA histone structure to reduce their transcription.
Retrotransposon | Role in human disease
In 1998, UMMS researcher Craig Mello (an investigator at the Howard Hughes Medical Institute) and his colleague Andrew Fire (of Stanford University, then of the Carnegie Institution in Washington, D.C.) discovered RNA interference (RNAi). They demonstrated that small pieces of double-stranded RNA had interfered with the expression of a gene whose coding sequence of DNA was similar to that of the RNA they tested. Mello and Fire received the 2006 Nobel Prize in Physiology or Medicine for their discoveries related to RNA interference. Federal and private research grants and contracts at UMMS rose from about $2 million in 1977 to more than $250 million in 2019.
University of Massachusetts Medical School | Research
Scherrer obtained his PhD in biochemistry from Swiss Institute of Technology, Zurich (ETH). He worked as a research assistant for James Darnell at MIT, where in 1962 he discovered the existence of giant pre-ribosomal and pre-messenger RNA in animal cells, and observed for the first time the processing of pre-ribosomal RNA (pre-rRNA) into functional rRNA. These discoveries made it possible to understand a fundamental process in nucleated cells, the synthesis of precursor RNA that is then metabolized in order to extract the information to be expressed. With Sheldon Penman, he demonstrated the existence of messenger RNA in polyribosomes. In 1963, he joined François Gros at the Institut Pasteur and, later, at the Institut de biologie physico-chimique (IBPC) in Paris, before founding in 1967, the molecular biology department at the Swiss Institute for Experimental Cancer Research (ISREC) in Lausanne.
Klaus Scherrer | Biography
Alzheimer disease 16 is a protein that in humans is encoded by the AD16 gene.
AD16 (gene) | Introduction
She also maintained an interest in the genetics of neurodegenerative diseases. Ridley was involved in early work on transmissible spongiform encephalopathy (subsequently known as prion disease), particularly in the recognition that individual cases of human prion disease could be sporadic, familial or acquired and that familial cases were associated with mutations in the prion protein gene. She demonstrated the transmissibility of bovine spongiform encephalopathy (BSE) and scrapie to primates and argued that the evidence for BSE and scrapie being acquired by maternal transmission was also compatible with genetic susceptibility to disease. In experiments using data extending over 25 years, she demonstrated that the amyloid proteins found in Alzheimer's disease were self-assembling and experimentally transmissible, establishing a link in pathogenesis between prion diseases and the other neurodegenerative proteinopathies Ridley's current research lies in aspects of cognitive psychology to be found in late nineteenth and early twentieth century books for children, especially the works of J.
Rosalind Ridley | Research
All organisms studied contain many RNases of two different classes, showing that RNA degradation is a very ancient and important process. As well as cleaning of cellular RNA that is no longer required, RNases play key roles in the maturation of all RNA molecules, both messenger RNAs that carry genetic material for making proteins, and non-coding RNAs that function in varied cellular processes. In addition, active RNA degradation systems are a first defense against RNA viruses, and provide the underlying machinery for more advanced cellular immune strategies such as RNAi. Some cells also secrete copious quantities of non-specific RNases such as A and T1.
Ribonuclease | Function
snRNP70 also known as U1 small nuclear ribonucleoprotein 70 kDa is a protein that in humans is encoded by the "SNRNP70" gene. snRNP70 is a small nuclear ribonucleoprotein that associates with U1 spliceosomal RNA, forming the U1snRNP a core component of the spliceosome. The U1-70K protein and other components of the spliceosome complex form detergent-insoluble aggregates in both sporadic and familial human cases of Alzheimer's disease. U1-70K co-localizes with Tau in neurofibrillary tangles in Alzheimer's disease.
SnRNP70 | Introduction
In the early 1980s, Brosius became interested in a small brain-specific RNA that was thought to be a waste product of a mechanism orchestrating the expression of genes by RNA polymerase III transcription of identifier sequence (ID) repetitive elements, classified as SINEs, short interspersed repeats, located in the introns of brain-specific genes by making chromatin accessible to RNA polymerase II. This attractive hypothesis was not tenable. Instead, the Brosius laboratory focused on this brain cytoplasmic BC1 RNA, cloned it as cDNA by developing a method for generating cDNA libraries based on non-polyadenylated RNAs, and isolated its single gene, which evolved from a retroposed copy of a transfer RNA (tRNA).
Jürgen Brosius | Scientific contributions
The RNA world hypothesis states that RNA was once both the carrier of hereditary information and enzymatically active, with different sequences acting as biocatalysts, regulators and sensors. The hypothesis then proposes that modern DNA, RNA and protein-based life evolved and selection replaced the majority of RNA's roles with other biomolecules. RNA thermometers and riboswitches are thought to be evolutionarily ancient due to their wide-scale distribution in distantly-related organisms. It has been proposed that, in the RNA world, RNA thermosensors would have been responsible for temperature-dependent regulation of other RNA molecules. RNA thermometers in modern organisms may be molecular fossils which could hint at a previously more widespread importance in an RNA world.
RNA thermometer | Implications for the RNA world hypothesis
In 1975, she published a research finding for which she is widely known, demonstrating that ribosomes use complementary base pairing to identify the start site on mRNA. In 1980, Steitz in collaboration with Michael Lerner published another critical paper, using immunoprecipitation with human antibodies from patients with autoimmunity to isolate and identify the novel entities snRNPs (pronounced "snurps") and detect their role in splicing. A snRNP is a specific short length of RNA, around 150 nucleotides long, associated with protein, that is involved in splicing introns out of newly transcribed RNA (pre-mRNA), a component of the spliceosomes. Steitz's paper "set the field ahead by light years and heralded the avalanche of small RNAs that have since been discovered to play a role in multiple steps in RNA biosynthesis," noted Susan Berget.
Joan A. Steitz | Career
The discovery of catalytic RNA (ribozymes) showed that RNA could both encode genetic information (like DNA) and catalyze specific biochemical reactions (like protein enzymes). This realization led to the RNA World Hypothesis, a proposal that RNA may have played a critical role in prebiotic evolution at a time before the molecules with more specialized functions (DNA and proteins) came to dominate biological information coding and catalysis. Although it is not possible for us to know the course of prebiotic evolution with any certainty, the presence of functional RNA molecules with common ancestry in all modern-day life forms is a strong argument that RNA was widely present at the time of the last common ancestor.
History of RNA biology | RNA was likely critical for prebiotic evolution
Since RNA degrades after death, a fresh brain is optimal – but not always available. This in turn can influence a variety of downstream analyses. Consideration should be taken of the following factors when working with 'omics data collected from post-mortem brains: Differential diagnosis also remains a critical pre-analytical confounder of cohort-wide studies of spectrum neurological disorders. Specifically, this has been noted to be a cromulant problem for Alzheimers disease and autism spectrum disorder studies. Furthermore, as our understanding of the diverse symptoms and genomic underpinnings of various neurogenomic disorders improves, the diagnostic criteria itself undergoes rearrangements and review.
Neurogenomics | In humans
Misfolded TDP-43 is found in the brains of older adults over age 85 with limbic-predominant age-related TDP-43 encephalopathy, (LATE), a form of dementia. HIV-1, the causative agent of acquired immunodeficiency syndrome (AIDS), contains an RNA genome that produces a chromosomally integrated DNA during the replicative cycle. Activation of HIV-1 gene expression by the transactivator "Tat" is dependent on an RNA regulatory element (TAR) located "downstream" (i.e. to-be transcribed at a later point in time) of the transcription initiation site. Mutations in the "TARDBP" gene are associated with neurodegenerative disorders including frontotemporal lobar degeneration and amyotrophic lateral sclerosis (ALS). In particular, the TDP-43 mutants M337V and Q331K are being studied for their roles in ALS.
TARDBP | Clinical significance
Recent recognition that long ncRNAs function in various aspects of cell biology has focused increasing attention on their potential to contribute towards disease etiology. More than 80% (1502 among 1867 lncRNAs in LncBook) experimentally studied lncRNAs have been reported to be associated with 462 diseases and 28 MeSH disease terms, and 97,998 lncRNAs are potentially associated with diseases based on the multi-omics evidence. A handful of studies have implicated long ncRNAs in a variety of disease states and support an involvement and co-operation in neurological disease and cancer. The first published report of an alteration in lncRNA abundance in aging and human neurological disease was provided by Lukiw et al.
Long non-coding RNA | In aging and disease
Adenosine deaminase acting on RNA (ADAR) and its gene were first discovered accidentally in 1987 as a result of research by Brenda Bass and Harold Weintraub. These researchers were using antisense RNA inhibition to determine which genes play a key role in the development of Xenopus laevis embryos. Previous research on Xenopus oocytes had been successful. However, when Bass and Weintraub applied identical protocols to Xenopus embryos, they were unable to determine the embryo’s developmental genes. In an attempt to understand why the method was unsuccessful, they began comparing duplex RNA in both oocytes and embryos. This led them to discover that a developmentally regulated activity denatures RNA:RNA hybrids in embryos.
ADAR | Discovery
Numerous key discoveries in biology have emerged from studies of RNA (ribonucleic acid), including seminal work in the fields of biochemistry, genetics, microbiology, molecular biology, molecular evolution and structural biology. As of 2010, 30 scientists have been awarded Nobel Prizes for experimental work that includes studies of RNA. Specific discoveries of high biological significance are discussed in this article. For related information, see the articles on History of Molecular Biology and History of Genetics. For background information, see the articles on RNA and nucleic acid.
History of RNA biology | Introduction
REST expression strongly correlates with increased longevity. REST levels are highest in the brains of people who lived up to be 90 - 100s and remained cognitively intact. Levels stayed high specifically in the brain regions vulnerable to Alzheimer's, suggesting that they might be protected from dementia. It is assumed that REST represses genes that promote cell death and Alzheimer's disease pathology, and induces the expression of stress response genes. Moreover, REST potently protects neurons from oxidative stress and amyloid β-protein toxicity. REST is also responsible for ischaemia induced neuronal cell death, in mouse models of brain ischaemia. Ischaemia, which results from reduced blood profusion of tissues, decreasing nutrient and oxygen supply, induces REST transcription and nuclear accumulation, leading to the epigenetic repression of neuronal genes leading to cell death.
RE1-silencing transcription factor | Function
Tsai observed that a truncated version of p35 called p25 accumulated in diseased or damaged brain tissue in mice and in tissue samples from deceased Alzheimer’s patients. In an experiment with genetically-engineered mice, Tsai found that increased expression of CDK5 led to the development of Alzheimer’s-like symptoms such as a decline in learning and cognition, profound neural loss in the forebrain, and that amyloid plaques developed within weeks. After moving to MIT in 2006, Tsai began to investigate how to ameliorate or reverse Alzheimer’s symptoms. In a 2007 study, Tsai trained mice to find and remember a platform submerged in a murky pool.
Li-Huei Tsai | Research
The cause of these diseases has been found to conventionally be expanded repetitions of CNG or NCNG nucleotide sequences in non-coding RNA. For example, myotonic dystrophy type 1 (DM1) results from the repetition of RNA base pairs CUG transcribed from a region of the DMPK gene, while myotonic dystrophy type 2 (DM2) is derived from an expanded CCUG sequence repeat. Similarly, FXTAS results from CGG repeats transcribed from a region in the FMR1 gene encoding protein, and spinocerebellar ataxia (SCA) results from CAG repetition transcribed in various genes. Furthermore, frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) have been found to develop from the repeated GGGGCC sequence transcribed from an intron in the "C90RF72" gene.
RNA-dominant disease | Cause
The "abiF" RNA motif is a conserved RNA structure that was discovered by bioinformatics.
AbiF RNA motif | Introduction
In September 1929 he joined the Rockefeller Institute. In 1930, he discovered the process of cell fractionation, which was groundbreaking in his time. The process consists of grinding up cells to break the membrane and release the cell's contents. He then filtered out the cell membranes and placed the remaining cell contents in a centrifuge to separate them according to mass. He divided the centrifuged contents into fractions, each of a specific mass, and discovered that particular fractions were responsible for particular cell functions. In 1938 he identified and purified for the first time component of Rous sarcoma virus, the causal agent of carcinoma, as "ribose nucleoprotein" (eventually named RNA).
Albert Claude | Career
Bookheimer contributed to understanding of Alzheimer's disease by investigated a common polymorphism, APOE-4, a risk gene for Alzheimer’s Disease. Her work showed that normal volunteers who differ in their possession of the risk polymorphism had different brain activation patterns from APOE-4 carriers.
Susan Y. Bookheimer | Research
Inaugural Article: Efficient reversal of Alzheimer's disease fibril formation and elimination of neurotoxicity by a small molecule Barbara J. Blanchard, Albert Chen, Leslie M. Rozeboom, Kate A. Stafford, Peter Weigele, and Vernon M. Ingram PNAS 2004 101: 14326-14332
Vernon Ingram | Selected publications
In his "Biology and Knowledge" (1967+ / French 1965), Piaget tentatively hinted at possible physical embodiments for his abstract schema entities. At the time, there was much talk and research about RNA as such an agent of learning, and Piaget considered some of the evidence. However, he did not offer any firm conclusions, and confessed that this was beyond his area of expertise. One difficulty at that time was that it was generally assumed that nearly all RNA served as mere templates for protein production, and such ideas offered no coherent explanation for Piaget's schema account. However (from 2001 onward), Mattick and others pointed out that, in humans, only about 3% of RNA serves that purpose! – leaving ample stocks of ncRNA available for other tasks (perhaps acting in their own right, rather than as templates).
Jean Piaget | Physical microstructure of schemata
The labs of Andrew Fire and Craig Mello had just demonstrated a key role for double-stranded RNA as the trigger for RNAi in the nematode "Caenorhabditis elegans", a discovery culminating in a Nobel Prize for Fire and Mello in 2006. By showing that RNAi also existed in another animal species, the Carthew group stimulated the search for RNAi in mammals, as well as the adoption of "Drosophila" as a premier model to study the biochemical and genetic mechanisms of RNAi. The Carthew group also developed the first and second generations of transgene systems for performing RNAi against any "Drosophila" gene at any stage of the life cycle in a tissue- or cell-specific manner.
Richard Carthew | Faculty career
As a typical example, this hypothesis explains the APOE risk locus of AD in context of signaling of its giant lipoprotein receptor, LRP1b which is a large tumor-suppressor gene with brain-specific expression and also maps to an unstable chromosomal fragile site. The large gene instability hypothesis puts the DNA damage mechanism at the center of Alzheimer's disease pathophysiology.
Biochemistry of Alzheimer's disease | Large gene instability hypothesis
Ribonucleases (RNases) protein family involved mainly in RNA metabolism, playing essential roles in RNA maturation, RNA end-turnover, and the degradation of aberrant RNAs or expired species in the cell. They are classified into exoribonucleases and endoribonucleases based on their degradative activities. Ribonuclease E (RNase E) was initially discovered as an endoribonuclease from "Escherichia coli" strain K12. Based on DNA sequence analysis, orthologs of E. coli RNase E were predicted to exist among dozens of evolutionarily different bacterial species. In E. coli, the ribonuclease E enzyme plays an essential part in controlling cell viability by regulating RNA metabolism, such as the decay of most mRNAs and activates the processing of pre-tRNAs.
Ribonuclease E | Evolutionary history
Previous studies have shown that SOAT modulates proteolytic processing in cell-based and animal models of Alzheimer's disease. A follow-up study reports that SOAT1 RNAi reduced cellular SOAT1 protein and cholesteryl ester levels while causing a slight increase in free cholesterol content of endoplasmic reticulum membranes. The data also showed that a modest decrease in SOAT activity led to suppressive effects on Abeta generation.
Sterol O-acyltransferase | SOAT1 (ACAT1)
An experimental system was developed in which an intron-containing rRNA precursor from the nucleus of the ciliated protozoan Tetrahymena could be spliced "in vitro". Subsequent biochemical analysis shows that this group I intron was self-splicing; that is, the precursor RNA is capable of carrying out the complete splicing reaction in the absence of proteins. In separate work, the RNA component of the bacterial enzyme ribonuclease P (a ribonucleoprotein complex) was shown to catalyze its tRNA-processing reaction in the absence of proteins. These experiments represented landmarks in RNA biology, since they revealed that RNA could play an active role in cellular processes, by catalyzing specific biochemical reactions.
History of RNA biology | Discovery of catalytic RNA (ribozymes)
Genetic variation in ERβ is both sex and age dependent and ERβ polymorphism can lead to accelerated brain aging, cognitive impairment, and development of AD pathology. Similar to CVD, post-menopausal women have an increased risk of developing Alzheimer's disease (AD) due to a loss of estrogen, which affects proper aging of the hippocampus, neural survival and regeneration, and amyloid metabolism. ERβ mRNA is highly expressed in hippocampal formation, an area of the brain that is associated with memory. This expression contributes to increased neuronal survival and helps protect against neurodegenerative diseases such as AD. The pathology of AD is also associated with accumulation of amyloid beta peptide (Aβ).
Estrogen receptor beta | Alzheimer's disease
Goate's research centers on the genetics of Alzheimer's disease and related dementias that led to the development of animal and cellular models and the development of anti-amyloid and anti-tau therapies. She has been the principal investigator on four grants and has co-invented and granted six patents.
Alison Goate | Research
He received his undergraduate training at the Université de Montréal in biochemistry and clinical sciences. Shortly after, he joined Dr. André Barbeau’s group at the Clinical Research Institute of Montréal where he worked on the neurobiology of Parkinson's disease. He then moved to the Alzheimer’s Disease Research Consortium of Southern California which is based at the Andrus Gerontology Centre, in Los Angeles. It is in California that he discovered the important role of apolipoprotein E, a cholesterol transporter that acts as a powerful modulator of brain reinnervation and a key player in Alzheimer's disease pathophysiology. In 1989, McGill University and the Douglas Institute recruited him back to Montréal to establish a research program specialized in the molecular biology of neurodegenerative diseases.
Judes Poirier | Career
Gary Bruce Ruvkun (born 26 March 1952, Berkeley, California) is an American molecular biologist at Massachusetts General Hospital and professor of genetics at Harvard Medical School in Boston. Ruvkun discovered the mechanism by which "lin-4", the first microRNA (miRNA) discovered by Victor Ambros, regulates the translation of target messenger RNAs via imperfect base-pairing to those targets, and discovered the second miRNA, "let-7", and that it is conserved across animal phylogeny, including in humans. These miRNA discoveries revealed a new world of RNA regulation at an unprecedented small size scale, and the mechanism of that regulation. Ruvkun also discovered many features of insulin-like signaling in the regulation of aging and metabolism.
Gary Ruvkun | Introduction
Later in the 1980s, Keene identified RNA recognition motif (RRM) proteins. RRM proteins are the largest family of RNA-binding proteins and the seventh largest protein family of the human genome. RRM is a prevalent RNA-binding fold involving proteins implicated in RNA biogenesis, processing, transport, and degradation.
Jack D. Keene | Research
A study looked at the involvement of RNA editing in RNA degradation. The researchers specifically looked at the interaction between ADAR and UPF1, an enzyme involved in the nonsense-mediated mRNA decay pathway (NMD). They found that ADAR and UPF1 are found within the suprasliceosome and they form a complex that leads to the down-regulation of specific genes. The exact mechanism or the exact pathways that these two are involved in are unknown at this time. The only fact that this research has shown is that they form a complex and down-regulate specific genes.
RNA editing | RNA editing may be involved in RNA degradation
This has helped advance methods for predicting RNA structure from sequence, as well as RNA-RNA interactions: e.g. miRNA or siRNA target binding. Methods using the "Turner Rules" are widely used by biochemists and biologists. In his own lab, these methods were used to discover potentially medically important RNA structures in influenza virus including an RNA pseudoknot that may play a role in regulating splicing at the Influenza A Segment 7 3' Splice Site. Recently, Doug and collaborators have used Nuclear Magnetic Resonance and Molecular Dynamics simulations of short RNAs to test understanding of the sequence dependence of stacking interactions. Much remains to be discovered.
Douglas H. Turner | Professional life and scientific achievements
These organisms or biological entities, these progenotes (or ribocytes), had RNA as informational molecule instead of DNA. RNA is capable of both catalysis and replication and could have been central to the origins of heredity and life itself. It has been proposed that the initial molecular events were carried out by transfer RNAs (tRNAs). It is hypothesized that structured tRNAs could have provided amino acids during a process called self-translation of a single extended tRNA strand.
Darwinian threshold | Before the Darwinian threshold
The physiological role of this processing is unclear, though it may play a role in nervous system development. Numerous in vitro and in vivo studies have shown correlations between IDE, Aβ degradation, and Alzheimer’s disease. Mice engineered to lack both alleles of the IDE gene exhibit a 50% decrease in Aβ degradation, resulting in cerebral accumulation of Aβ. Studies of genetically inherited forms of Alzheimer’s show reduction in both IDE expression and catalytic activity among affected individuals. Despite the evident role of IDE in disease, relatively little is known about its physiological functions. These may be diverse, as IDE has been localized to several locations, including the cytosol, peroxisomes, endosomes, proteasome complexes, and the surface of cerebrovascular endothelial cells.
Insulin-degrading enzyme | Alzheimer's disease
Aloysius Alzheimer (also known as Alois Alzheimer; ; ; 14 June 1864 – 19 December 1915) was a German psychiatrist and neuropathologist and a colleague of Emil Kraepelin. Alzheimer is credited with identifying the first published case of "presenile dementia", which Kraepelin would later identify as Alzheimer's disease.
Alois Alzheimer | Introduction
Organic chemist Donna Blackmond described this finding as "strong evidence" in favour of the RNA world. However, John Sutherland said that while his team's work suggests that nucleic acids played an early and central role in the origin of life, it did not necessarily support the RNA world hypothesis in the strict sense, which he described as a "restrictive, hypothetical arrangement".
RNA world | Support and difficulties
The research project was awarded the ERC Advanced Investigator Grant by the European Research Council in 2011. Work following this hypothesis led to the development of the “RNA Interactome Capture” technique and to the discovery of hundreds of formerly unknown RNA-binding proteins in the cells of living organisms from human to yeast, including more than 50 metabolic enzymes. Recently, Hentze and his colleagues discovered new RNA-binding motives of proteins which they unraveled using a newly developed method called “RBDmap”. In 2019, they described the concept of riboregulation. They found out that the autophagy receptor protein p62 is directly regulated by a small RNA, vtRNA1-1.
Matthias Hentze | Research
In November 2012, Schubert et al. revealed that specific RNAs control chromatin compaction and accessibility in "Drosophila" cells.
Small nucleolar RNA | Other functions
The RNA world hypothesis, if true, has important implications for the definition of life. For most of the time that followed Watson and Crick's elucidation of DNA structure in 1953, life was largely defined in terms of DNA and proteins: DNA and proteins seemed the dominant macromolecules in the living cell, with RNA only aiding in creating proteins from the DNA blueprint. The RNA world hypothesis places RNA at center-stage when life originated. The RNA world hypothesis is supported by the observations that ribosomes are ribozymes: the catalytic site is composed of RNA, and proteins hold no major structural role and are of peripheral functional importance.
RNA world | Implications
It is also likely that many ncRNAs are non functional (sometimes referred to as junk RNA), and are the product of spurious transcription. Non-coding RNAs are thought to contribute to diseases including cancer and Alzheimer's.
Non-coding RNA | Introduction
In this disease, there is a build of the amyloid beta protein in the brain. This ultimately leads to a reduction in the haemodynamic response and less blood flow in the brain. This reduced cerebral blood flow not only kills neuronal cells because of shortages in oxygen and glucose but it also reduces the brain's ability to remove amyloid beta. In a healthy brain, these protein fragments are broken down and eliminated. In Alzheimer's disease, the fragments accumulate to form hard, insoluble plaques which reduce blood flow. Two proteins are involved in this accumulation of amyloid beta: serum response factor or SRF and myocardin.
Haemodynamic response | Alzheimer's disease
In addition to its crucial role in cancer, p53 has been implicated in other diseases including diabetes, cell death after ischemia, and various neurodegenerative diseases such as Huntington, Parkinson, and Alzheimer. Studies have suggested that p53 expression is subject to regulation by non-coding RNA.
Non-coding RNA | Cancer
To further distinguish age-related memory loss from Alzheimer's disease (AD), a subregion of the hippocampal formation called the dentate gyrus (DG) was further studied, since it is thought to be targeted by aging. Human postmortem tissue was collected from both DG and entorhinal cortex (EC). Entorhinal cortex is a neighboring subregion unaffected by aging and known to be implicated in age-related memory loss. After normalizing the expression of EC, 17 genes were manifested due to age-related changes in the DG. Mice were used as the experimental subjects to test whether the decline of RbAp48 was also related to age-related memory loss.
Deficiency of RbAp48 protein and memory loss | Experimental process
Gerbi received her PhD from Yale University in 1970 for her work with Joseph Gall; she and Gall developed the technique of in situ hybridization, which is used to localize RNA or DNA in tissue. After earning her doctorate, she completed a fellowship at the Max Planck Institute before returning to the United States and establishing her own laboratory. Between 1998 and 2001, she published research detailing a method to determine the nucleotide where DNA replication begins for a gene and showed that in yeast and other eukaryotes, this site is adjacent to the origin recognition complex binding site. Her recent research has covered conservation of ribosomal RNA sequences between prokaryotes and eukaryotes, as well as the role of small nucleolar RNA (a subset of small nuclear RNA) during ribosomal RNA post-translational modification.
Susan Gerbi | Research career
The oldest hypothesis is the "cholinergic hypothesis". It states that Alzheimer's begins as a deficiency in the production of acetylcholine, a vital neurotransmitter. Much early therapeutic research was based on this hypothesis, including restoration of the "cholinergic nuclei". The possibility of cell-replacement therapy was investigated on the basis of this hypothesis. All of the first-generation anti-Alzheimer's medications are based on this hypothesis and work to preserve acetylcholine by inhibiting acetylcholinesterases (enzymes that break down acetylcholine). These medications, though sometimes beneficial, have not led to a cure. In all cases, they have served to only treat symptoms of the disease and have neither halted nor reversed it.
Biochemistry of Alzheimer's disease | Cholinergic hypothesis
Her research involves cancer genetics and adult genetics such inherited immune disorders, stroke, cancer, heart disease and etiology. Her highest cited paper is "Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease" at 1080 times, according to Google Scholar.
Gail Jarvik | Research