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
Friedrich Miescher Sorry. I cannot find the answer based on the context. Jeannie T. Lee. Robert W. Holley "et al."
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
Mello and Andrew Fire the 2006 Nobel Prize in Physiology or Medicine. Recent discoveries of ncRNAs have been achieved through both experimental and bioinformatic methods.
Non-coding RNA | History and discovery
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
Nucleic acids were first discovered in 1868 by Friedrich Miescher and by 1939 RNA had been implicated in protein synthesis. Two decades later, Francis Crick predicted a functional RNA component which mediated translation; he reasoned that RNA is better suited to base-pair with an mRNA transcript than a pure polypeptide. The first non-coding RNA to be characterised was an alanine tRNA found in baker's yeast, its structure was published in 1965. To produce a purified alanine tRNA sample, Robert W. Holley "et al." used 140kg of commercial baker's yeast to give just 1g of purified tRNA for analysis. The 80 nucleotide tRNA was sequenced by first being digested with Pancreatic ribonuclease (producing fragments ending in Cytosine or Uridine) and then with takadiastase ribonuclease Tl (producing fragments which finished with Guanosine).
Non-coding RNA | History and discovery
Molecular analysis of mRNA molecules showed that, following transcription, mRNAs have non-DNA-encoded nucleotides added to both their 5′ and 3′ ends (guanosine caps and poly-A, respectively). Enzymes were also identified that add and maintain the universal CCA sequence on the 3′ end of tRNA molecules. These events are among the first discovered examples of RNA processing, a complex series of reactions that are needed to convert RNA primary transcripts into biologically active RNA molecules.
History of RNA biology | Non-encoded nucleotides are added to the ends of RNA molecules
These statistics were combined using a support vector machine. Other properties include the appearance of a promoter to transcribe the RNA. ncRNAs are also often followed by a Rho-independent transcription terminator.
Bioinformatics discovery of non-coding RNAs | Discovery by general properties
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
Chromatography and identification of the 5' and 3' ends then helped arrange the fragments to establish the RNA sequence. Of the three structures originally proposed for this tRNA, the 'cloverleaf' structure was independently proposed in several following publications. The cloverleaf secondary structure was finalised following X-ray crystallography analysis performed by two independent research groups in 1974. Ribosomal RNA was next to be discovered, followed by URNA in the early 1980s. Since then, the discovery of new non-coding RNAs has continued with snoRNAs, Xist, CRISPR and many more. Recent notable additions include riboswitches and miRNA; the discovery of the RNAi mechanism associated with the latter earned Craig C.
Non-coding RNA | History and discovery
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
Next to be linked to regulation were Xist and other long noncoding RNAs associated with X chromosome inactivation. Their roles, at first mysterious, were shown by Jeannie T. Lee and others to be the silencing of blocks of chromatin via recruitment of Polycomb complex so that messenger RNA could not be transcribed from them. Additional lncRNAs, currently defined as RNAs of more than 200 base pairs that do not appear to have coding potential, have been found associated with regulation of stem cell pluripotency and cell division.
RNA | Long non-coding RNAs
This insight separated the coding function from structural constraints as proposed in a clever code by George Gamow. This led Francis Crick to propose the concept of the adaptor or as it is now known "transfer RNA (tRNA)". The physical separation between the anticodon and the amino acid on a tRNA is the basis for the unidirectional flow of information in coded biological systems. This is commonly known as the central dogma of molecular biology i.e. that information flows from nucleic acid to protein and never from protein to nucleic acid. Following this adaptor insight, Brenner proposed the concept of a messenger RNA, based on correctly interpreting the work of Elliot "Ken" Volkin and Larry Astrachan.
Sydney Brenner | Career and research
Some properties are shared by multiple unrelated classes of ncRNA, and these properties can be targeted to discover new classes. Chief among them is the conservation of an RNA secondary structure. To measure conservation of secondary structure, it is necessary to somehow find homologous sequences that might exhibit a common structure. Strategies to do this have included the use of BLAST between two sequences or multiple sequences, exploited synteny via orthologous genes or used locality sensitive hashing in combination with sequence and structural features. Mutations that change the nucleotide sequence, but preserve secondary structure are called covariation, and can provide evidence of conservation.
Bioinformatics discovery of non-coding RNAs | Discovery by general properties
Cech's main research area is that of the process of transcription in the nucleus of cells. He studies how the genetic code of DNA is transcribed into RNA. In the 1970s, Cech had been studying the splicing of RNA in the unicellular organism "Tetrahymena thermophila" when he discovered that an unprocessed RNA molecule could splice itself. In 1982, Cech became the first to show that RNA molecules are not restricted to being passive carriers of genetic information – they can have catalytic functions and can participate in cellular reactions. RNA-processing reactions and protein synthesis on ribosomes in particular are catalysed by RNA.
Thomas Cech | Research
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
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
One of his current research directions includes incorporating research on noncoding RNA, such as siRNA or hairpin RNA isolated by combining forward genetics and genomic screens. He has used this technique on miRNA to examine signalling and cell survival.
John B. Hogenesch | Non-coding RNA and functional genomics
After completing his postdoctoral position with Dr. Susan Berget at Baylor College of Medicine in Biochemistry in 1986, Smith became an assistant professor at the University of Rochester. Between 1991-1994, Smith discovered the molecular mechanism by which proteins recognize messenger RNA and participate in site-specific assembly of enzyme complexes to orchestrate the modification of select cytidines to uridines in a process known as C to U RNA Editing. This work has served as the foundation for numerous findings concerning RNA sequence modifying mechanisms and DNA mutating mechanisms that determine cell and protein diversification and was cited for its groundbreaking ideas in an article written by L.
Harold Smith (scientist) | Career
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
Natasha Jane Caplen is a British-American geneticist who discovered RNA interference (RNAi) in mammalian cells. She is a senior investigator and head of the functional genetics section at the National Cancer Institute.
Natasha J. Caplen | Introduction
Another previously unknown mechanism by which RNA molecules are involved in genetic regulation was discovered in the 1990s. Small RNA molecules termed microRNA (miRNA) and small interfering RNA (siRNA) are abundant in eukaryotic cells and exert post-transcriptional control over mRNA expression. They function by binding to specific sites within the mRNA and inducing cleavage of the mRNA via a specific silencing-associated RNA degradation pathway.
History of RNA biology | Small RNA molecules regulate gene expression by post-transcriptional gene silencing
The research group Salzman et al. originally wanted to identify cancer-specific exon scrambling events. They ended up finding scrambled exons in a large number of normal and cancer cells. They discovered that scrambled exon isoforms comprised about 10% of total transcript isoforms in leukocytes. They also identified 2,748 scrambled isoforms in HeLa and H9 embryonic stem cells. They found that about 1 in 50 expressed genes produced scrambled transcript isoforms at least 10% of the time. Some of the tests for circularity included: (1) Treated samples with RNase R, an enzyme which degrades linear RNAs but not circular RNAs, and (2) Tested for the presence of poly-A tails (shouldn't be present in a circular molecule).
Circular RNA | Salzman et al. 2012
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
By 1958, experiments and analysis such as the Avery–MacLeod–McCarty experiment, the Hershey–Chase experiment, the and the Meselson–Stahl experiment had shown DNA to be the molecule of genetic information. It was not known, however, how DNA directed the expression of proteins, or what role RNA had in these processes. Nirenberg teamed up with Heinrich J. Matthaei at the National Institutes of Health to answer these questions. They produced RNA composed solely of uracil, a nucleotide that only occurs in RNA. They then added this synthetic poly-uracil RNA into a cell-free extract of "Escherichia coli" which contained the DNA, RNA, ribosomes and other cellular machinery for protein synthesis.
Marshall Warren Nirenberg | Research
During the next decade, molecular biology the world over flourished, the outline bones of the 1950s now having flesh put on them. The detailed 3-D atomic structures of a series of proteins, and how they function, were deduced. These included myoglobin, hemoglobin and chymotrypsin, the last by David Blow. The genetic code, from evidence around the world, was assembled by Crick. Punctuation signals in the messenger RNA — where to start translating the RNA into a protein sequence, and where to stop — were discovered by postdoctoral fellow Joan A. Steitz. Crick suggested how the tRNA molecules — his original adaptors — read the messenger in his wobble hypothesis.
MRC Laboratory of Molecular Biology | Molecular Biology: after 1962
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
Early studies suggested a minimum of two RNAPs: one which synthesized rRNA in the nucleolus, and one which synthesized other RNA in the nucleoplasm, part of the nucleus but outside the nucleolus. In 1969, science experimentalists Robert Roeder and William Rutter definitively discovered an additional RNAP that was responsible for transcription of some kind of RNA in the nucleoplasm. The finding was obtained by the use of ion-exchange chromatography via DEAE coated Sephadex beads. The technique separated the enzymes by the order of the corresponding elutions, Ι,ΙΙ,ΙΙΙ, by increasing the concentration of ammonium sulfate. The enzymes were named according to the order of the elutions, RNAP I, RNAP II, RNAP IΙI.
RNA polymerase II | Discovery
The discovery of discontinuous genes and RNA splicing was entirely unexpected by the community of RNA biologists, and stands as one of the most shocking findings in molecular biology research.
History of RNA biology | Genes are commonly interrupted by introns that must be removed by RNA splicing
Uhlenbeck was first published in 1968 at Harvard University for an article titled, “Some Effects on Noncomplementary Bases on the Stability of Helical Complexes of Polyribonucleotides.” The study overviews the conformation of specific polyribonucleotide sequences. The group used synthetic polyribonucleotides with slight distortions and studied whether their conformations stayed in the helical formation or if they took on a new formation. They determined that some of the instability in formation could be due to the non-complementary bases or the bases directly next to those that are non-complementary. In the 1970’s, he began his work on RNA. Uhlenbeck published many articles on the structure of RNA and its properties.
Olke Uhlenbeck | Research topics
They added DNase, which breaks apart the DNA, so that no additional proteins would be produced other than that from their synthetic RNA. They then added 1 radioactively labeled amino acid, the building blocks of proteins, and 19 unlabeled amino acids to the extract, varying the labeled amino acid in each sample. Only in the extract containing the radioactively labeled phenylalanine, was the resulting protein also radioactive. This implied that the genetic code for phenylalanine on RNA consisted of a repetition of uracil bases. Indeed, as we know now, it is UUU (three uracil bases in a row). This was the first step in deciphering the codons of the genetic code and the first demonstration of messenger RNA (see "Nirenberg and Matthaei experiment").
Marshall Warren Nirenberg | Research
In November 2012, Schubert et al. revealed that specific RNAs control chromatin compaction and accessibility in "Drosophila" cells.
Small nucleolar RNA | Other functions
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
Lee joined the faculty at Harvard in 1997 and devoted her studies to noncoding RNA and sex chromosome dynamics during development and disease. Her major career research achievements include identifying the X inactivation center, discovering Tsix antisense RNA, determining Xist's mechanism of action, demonstrating that a lncRNA is a regulator of Polycomb repressive complex 2, and determining that the X chromosome folds like Origami and adopts a unique conformation. Her studies established the existence and function of a group of regulatory RNAs known as long noncoding RNAs or lncRNAs. There are about ten times as many lncRNAs in a eukaryotic cell as mRNAs.
Jeannie T. Lee | Research career
Fire and Mello were awarded the 2006 Nobel Prize in Physiology or Medicine for discovering microRNAs (miRNAs), specific short RNA molecules that can base-pair with mRNAs.
RNA | Regulatory RNA
In 2004 Hogenesch left California to become a professor and the Director of Genome Technology at The Scripps Research Institute's other location in West Palm Beach, FL, where he continued his work on transcriptomes. Hogenesch contributed to a study published in 2005 which used new RNAi genetic screening techniques to discover a non-coding RNA (ncRNA) known as NRON. NRON, a repressor of the protein NFAT, is one of the first well characterized examples of a ncRNAs involved in transcription regulation. In 2006, Hogenesch moved to the Perelman School of Medicine at the University of Pennsylvania where he continues to study mammalian circadian clocks and genome function.
John B. Hogenesch | Non-coding RNA and functional genomics
Harris and his colleagues developed some of the basic techniques for investigating and measuring genes along the human chromosome. In 1965, he reported his observation that most nuclear RNA was non-coding, a view that was not widely accepted until years later. In 1969, Harris showed that when malignant cancer cells were fused with normal fibroblasts, the resulting hybrids were not malignant, thus demonstrating the existence of genes that could suppress malignancy. Work on these tumour suppressor genes has become a worldwide industry.
Henry Harris (scientist) | Career
Although some fundamental facts were known about nucleic acids due to these early discoveries, its structure and function remained a mystery. It wasn’t until the discovery of nucleotides in 1919 by Phoebus Levene, a Russian-Lithuanian biochemist that re-opened the gates of the DNA discovery. Levene first identified the carbohydrate component present in yeast RNA was in fact ribose. However, it was not until his discovery that the carbohydrate component in thymus nucleic acid was also a sugar but lacked one oxygen atom, termed deoxyribose, that his discovery was widely appreciated by the scientific community. Eventually, Levene was able to identify the correct order of which the components of RNA and DNA are put together, a phosphate-sugar-base unit, in which he later called a nucleotide.
Ribonucleotide | History
Before these discoveries, it was believed that biological catalysis was solely the realm of protein enzymes.
History of RNA biology | Discovery of catalytic RNA (ribozymes)
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
Sharp's current research focuses on small RNAs and other types of non-coding RNAs. His laboratory works to identify the target mRNAs of microRNAs (miRNAs), and has discovered a class of miRNAs that are produced from sequences adjacent to transcription start sites. His laboratory also studies how miRNA gene regulation functions in angiogenesis and cellular stress.
Phillip Allen Sharp | Research
One of his most cited articles is, “The Improved estimation of secondary structure in ribonucleic acids,” published in 1973. This study began a passion for RNA and the majority of his publications thereafter focused on it. He studied RNA binding sites and their synthesis. In 1987, he published another one of his most notable articles in the Oxford University Press. This article is called, “Oligoribonucleotide synthesis using T7 RNA polymerase and synthetic DNA templates.” They found that transcription occurs at variable initiation sites that can produce small nucleotide strands. These different strands contribute to the variability of RNA. The article has been cited over 2000 times in notable journal articles.
Olke Uhlenbeck | Research topics
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
In addition to their well-established roles in translation and splicing, members of noncoding RNA (ncRNA) families have recently been found to function in genome defense and chromosome inactivation. For example, piwi-interacting RNAs (piRNAs) prevent genome instability in germ line cells, while Xist (X-inactive-specific-transcript) is essential for X-chromosome inactivation in mammals.
History of RNA biology | Noncoding RNA controls epigenetic phenomena
RNA interference (RNAi) is a natural process used by cells to regulate gene expression. It was discovered in 1998 by Andrew Fire and Craig Mello, who won the Nobel Prize for their discovery in 2006. The process to silence genes first begins with the entrance of a double-stranded RNA (dsRNA) molecule into the cell, which triggers the RNAi pathway. The double-stranded molecule is then cut into small double-stranded fragments by an enzyme called Dicer. These small fragments, which include small interfering RNAs (siRNA) and microRNA (miRNA), are approximately 21–23 nucleotides in length. The fragments integrate into a multi-subunit protein called the RNA-induced silencing complex, which contains Argonaute proteins that are essential components of the RNAi pathway.
Gene silencing | RNA interference
At the IBPC, he studied the structure of giant RNA of the messenger type in cell differentiation (avian erythroblasts) and formulated the hypothesis of the existence of pre-messenger pre-mRNA by analogy to pre-rRNA.
Klaus Scherrer | Biography
The complex moves along through the untranslated region until it stalls just prior to reaching the start codon because it encounters a highly conserved sequence (a Kozak consensus sequence in eukaryotes, or Shine-Dalgarno sequence in prokaryotes). The stalled complex then combines with the large ribosome (60S) to begin translating the RNA into protein. Lechner invented the first riboregulator in 1991. Lechner used a self pairing stem-loop which inhibited translation of a prokaryotic RNA, unless a complementary RNA sequence (anti-inhibitor) was present. In 1997, Black engineered the first eukaryotic riboregulator using antisense molecules to prevent translation (Nucline RNA). In the Nucline system, antisense molecules block translation unless removed via competitive hybridization and strand-displacement by specific signal RNA sequences such as HIV RNA and oncogene RNA.
Riboregulator | Translational riboregulator
The concept of messenger RNA emerged during the late 1950s, and is associated with Crick's description of his "Central Dogma of Molecular Biology", which asserted that DNA led to the formation of RNA, which in turn led to the synthesis of proteins. During the early 1960s, sophisticated genetic analysis of mutations in the lac operon of E. coli and in the rII locus of bacteriophage T4 were instrumental in defining the nature of both messenger RNA and the genetic code. The short-lived nature of bacterial RNAs, together with the highly complex nature of the cellular mRNA population, made the biochemical isolation of mRNA very challenging.
History of RNA biology | Messenger RNA (mRNA) carries genetic information that directs protein synthesis
In 2006, Fire and Craig Mello shared the Nobel Prize in Physiology or Medicine for work first published in 1998 in the journal "Nature". Fire and Mello, along with colleagues SiQun Xu, Mary Montgomery, Stephen Kostas, and Sam Driver, reported that tiny snippets of double-stranded RNA (dsRNA) effectively shut down specific genes, driving the destruction of messenger RNA (mRNA) with sequences matching the dsRNA. As a result, the mRNA cannot be translated into protein. Fire and Mello found that dsRNA was much more effective in gene silencing than the previously described method of RNA interference with single-stranded RNA. Because only small numbers of dsRNA molecules were required for the observed effect, Fire and Mello proposed that a catalytic process was involved.
Andrew Fire | Nobel Prize
James Manley is Julian Clarence Levi Professor of Life Sciences at Columbia University, where his laboratory studies gene expression in mammalian cells. Manley and colleagues identified and characterized the key factors responsible for polyadenylation of mRNA precursors, and elucidated how this remarkably complex machinery functions in gene regulation, for example during cell growth and differentiation. He has also studied the mechanism and regulation of the process by which introns are removed from mRNA precursors, mRNA splicing. Manley and his coworkers codiscovered the first alternative splicing factor (SR protein), characterized how this and other splicing regulatory proteins function and are themselves regulated, showed how alternative splicing can become deregulated in disease, and with respect to mechanism demonstrated that two spliceosomal small nuclear RNAs by themselves have catalytic activity.
James L. Manley | Introduction
6C RNA is a class of non-coding RNA present in actinomycetes. 6C RNA was originally discovered as a conserved RNA structure having two stem-loops each containing six or more cytosine (C) residues. Later work revealed that 6C RNAs in "Streptomyces coelicolor" and "Streptomyces avermitilis" have predicted rho-independent transcription terminators, and microarray and reverse-transcriptase PCR experiments indicate that the "S. coelicolor" version is transcribed as RNA. Transcription of the "S. coelicolor" RNA increases during sporulation, and three transcripts were detected that overlap the 6C motif, but have different apparent start and stop sites. Additional work established that 6C RNAs regulate a variety of protein-coding genes by acting as "trans"-acting antisense RNAs.
6C RNA | Introduction
This problem was overcome in the 1960s by the use of reticulocytes in vertebrates, which produce large quantities of mRNA that are highly enriched in RNA encoding alpha- and beta-globin (the two major protein chains of hemoglobin). The first direct experimental evidence for the existence of mRNA was provided by such a hemoglobin synthesizing system.
History of RNA biology | Messenger RNA (mRNA) carries genetic information that directs protein synthesis
With Andrew Hamilton he discovered the small interfering RNA that is the specificity determinant in RNA-mediated gene silencing. Baulcombe's group demonstrated that while viruses can induce gene silencing, some viruses encode proteins that suppress gene silencing. After these initial observations in plants, many laboratories around the world searched for the occurrence of this phenomenon in other organisms. In 1998 Craig Mello and Andrew Fire reported a potent gene silencing effect after injecting double stranded RNA into "Caenorhabditis elegans". This discovery was particularly notable because it represented the first identification of the causative agent for the phenomenon. Fire and Mello were awarded the Nobel Prize in Physiology or Medicine in 2006 for their work.
David Baulcombe | Career and research
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
RNAP was discovered independently by Charles Loe, Audrey Stevens, and Jerard Hurwitz in 1960. By this time, one half of the 1959 Nobel Prize in Medicine had been awarded to Severo Ochoa for the discovery of what was believed to be RNAP, but instead turned out to be polynucleotide phosphorylase.
RNA polymerase | History
The SraC/RyeA RNA is a non-coding RNA that was discovered in "E. coli" during two large scale screens for RNAs. The function of this RNA is currently unknown. This RNA overlaps the SdsR/RyeB RNA on the opposite strand suggesting that the two RNAs may act in a concerted manner.
SraC/RyeA RNA | Introduction
The presence of allele-specific histone methylation at the Igf2r locus suggests Air also mediates silencing via chromatin modification.
Long non-coding RNA | Imprinting
Through the late 1950s and early 1960s, numerous papers were published on various topics in RNA structure, including RNA-DNA hybridization, triple stranded RNA, and even small-scale crystallography of RNA di-nucleotides - G-C, and A-U - in primitive helix-like arrangements. For a more in-depth review of the early work in RNA structural biology, see the article "The Era of RNA Awakening: Structural biology of RNA in the early years" by Alexander Rich.
History of molecular biology | Pre-history: the helical structure of RNA
His work with Torbjörn Caspersson showed that RNA plays an active role in protein synthesis. Brachet also carried out pioneering work in the field of cell differentiation. Brachet demonstrated that differentiation is preceded by the formation of new ribosomes and accompanied by the release from the nucleus of a wave of new messenger RNA.
Jean Brachet | Life
Noncoding RNAs belong to several groups and are involved in many cellular processes. These range from ncRNAs of central importance that are conserved across all or most cellular life through to more transient ncRNAs specific to one or a few closely related species. The more conserved ncRNAs are thought to be molecular fossils or relics from the last universal common ancestor and the RNA world, and their current roles remain mostly in regulation of information flow from DNA to protein.
Non-coding RNA | Biological roles
ChiRP-Seq (Chromatin Isolation by RNA purification) is a high-throughput sequencing method to discover regions of the genome which are bound by a specific RNA (or by a ribonucleoprotein containing the RNA of interest). Recent studies have shown that a significant proportion of some genomes (including mouse and human genomes) synthesize RNA that apparently do not code for proteins. The function of most of these non-coding RNA still has to be ascertained. Various genomic methods are being developed to map the functional association of these novel RNA to distinct regions of the genome to gain a better understanding of their function.
ChiRP-Seq | Introduction
The RNA-editing Guide RNA was discovered in 1990 by B. Blum, N. Bakalara, and L. Simpson because of their role in RNA editing in the mitochondrion of Leishmania tarentolae. These gRNA molecules are encoded in maxicircle DNA in mitochondria having sequences that are complementary to mature mRNAs within the edited regions. They participate in multiple activities to cleave, insert, or delete bases after the formation of partial hybrid between gRNA and pre-edited mRNA
Guide RNA | History
He and Basil Lythgoe proved this to be the case. He gained his second PhD in 1952. He later worked on the selective phosphorylation of nucleosides to form nucleotides. This was the beginning of a lifelong career, and led to the chemical structures of RNA and, by inference, DNA.
Daniel McGillivray Brown | Biography
A molecule that allows the genetic material to be realized as a protein was first hypothesized by François Jacob and Jacques Monod. Severo Ochoa won a Nobel Prize in Physiology or Medicine in 1959 for developing a process for synthesizing RNA "in vitro" with polynucleotide phosphorylase, which was useful for cracking the genetic code. RNA synthesis by RNA polymerase was established "in vitro" by several laboratories by 1965; however, the RNA synthesized by these enzymes had properties that suggested the existence of an additional factor needed to terminate transcription correctly. In 1972, Walter Fiers became the first person to actually prove the existence of the terminating enzyme.
Transcription (biology) | History
This discovery demonstrated that there was an additional enzyme present in the nucleoplasm, which allowed for the differentiation between RNAP II and RNAP III.
RNA polymerase II | Discovery
This non-coding RNA was discovered in the bacteria "Escherichia coli" during a large scale computational screen for transcription signals and genomic features of known small RNA-encoding genes. During this screen 14 novel ncRNA genes were identified, including GlmZ, SraB, SraC and SraD. The expression of SraH was experimentally confirmed by Northern blotting. Its expression is highly abundant in stationary growth phase but low levels of expression can still be detected in exponentially growing cells.
ArcZ RNA | Discovery
Their conclusion was that 98% of scrambled isoforms represented circRNAs. Zhang et al. 2014
Circular RNA | Salzman et al. 2012
All organisms have genes, which are coded by DNA, which is copied to RNA, which creates proteins, which are sequences of amino acids. DNA resides in the nucleus. When a cell expresses a gene, it copies (transcribes) that gene's DNA sequence onto a messenger RNA (mRNA) sequence. mRNA is transported out of the nucleus to ribosomes. The ribosomes read the mRNA and translate the code into the right amino acid sequence to make that gene's protein. The DNA is transcribed to mRNA by an enzyme, RNA polymerase II, with the help of many other proteins. Using yeast, Kornberg identified the role of RNA polymerase II and other proteins in transcribing DNA, and he created three-dimensional images of the protein cluster using X-ray crystallography.
Roger D. Kornberg | Research
In part because of heterogeneity of the samples tested, early fiber diffraction patterns were usually ambiguous and not readily interpretable. In 1955, Marianne Grunberg-Manago and colleagues published a paper describing the enzyme polynucleotide phosphorylase, which cleaved a phosphate group from nucleotide diphosphates to catalyze their polymerization. This discovery allowed researchers to synthesize homogenous nucleotide polymers, which they then combined to produce double stranded molecules. These samples yielded the most readily interpretable fiber diffraction patterns yet obtained, suggesting an ordered, helical structure for cognate, double stranded RNA that differed from that observed in DNA. These results paved the way for a series of investigations into the various properties and propensities of RNA.
History of molecular biology | Pre-history: the helical structure of RNA
The biochemical purification and characterization of RNA polymerase from the bacterium Escherichia coli enabled the understanding of the mechanisms through which RNA polymerase initiates and terminates transcription, and how those processes are regulated to regulate gene expression (i.e. turn genes on and off). Following the isolation of E. coli RNA polymerase, the three RNA polymerases of the eukaryotic nucleus were identified, as well as those associated with viruses and organelles. Studies of transcription also led to the identification of many protein factors that influence transcription, including repressors, activators and enhancers. The availability of purified preparations of RNA polymerase permitted investigators to develop a wide range of novel methods for studying RNA in the test tube, and led directly to many of the subsequent key discoveries in RNA biology.
History of RNA biology | RNA polymerase is purified
He computed that such mutations were occurring at the rate of roughly 0-5 per year per gamete. In later years, a new paradigm emerged, that placed RNA as a precursor molecule to DNA. A primordial molecule principle was put forth as early as 1968 by Crick, and lead to what is now known as The RNA World Hypothesis. DNA is found, predominantly, as fully base paired double helices, while biological RNA is single stranded and often exhibits complex base-pairing interactions. These are due to its increased ability to form hydrogen bonds, a fact which stems from the existence of the extra hydroxyl group in the ribose sugar.
Neutral network (evolution) | Mathematical Framework
SraG (small RNA G) is a small non-coding RNA (ncRNA). It is the functional product of a gene which is not translated into protein. This ncRNA was discovered in the bacteria "Escherichia coli" during a large scale computational screen for transcription signals and genomic features of known small RNA-encoding genes. During this screen 14 novel ncRNA genes were identified, including GlmZ, SraB, SraC and SraD. The expression of SraG was experimentally confirmed by Northern blotting which also indicated this RNA undergoes specific cleavage processing. The function of this RNA is unknown.
SraG RNA | Introduction
The C0719 RNA is a bacterial non-coding RNA of 222 nucleotides in length that is found between the "yghK" and "glcB" genes in the genomes of "Escherichia coli" and "Shigella flexneri". This non-coding RNA was originally identified in "E.coli" using high-density oligonucleotide probe arrays (microarray.) The function of this ncRNA is unknown.
C0719 RNA | Introduction
The genetic code consists of the translation of particular nucleotide sequences in mRNA to specific amino acid sequences in proteins (polypeptides). The ability to work out the genetic code emerged from the convergence of three different areas of study--(i) new methods to generate synthetic RNA molecules of defined composition to serve as artificial mRNAs, (ii) development of "in vitro" translation systems that could be used to translate the synthetic mRNAs into protein, and (iii) experimental and theoretical genetic work which established that the code was written in three letter "words" (codons). Today, our understanding of the genetic code permits the prediction of the amino sequence of the protein products of the tens of thousands of genes whose sequences are being determined in genome studies.
History of RNA biology | The genetic code is solved
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)
The biochemical identification of RISC was conducted by Gregory Hannon and his colleagues at the Cold Spring Harbor Laboratory. This was only a couple of years after the discovery of RNA interference in 1998 by Andrew Fire and Craig Mello, who shared the 2006 Nobel Prize in Physiology or Medicine. Hannon and his colleagues attempted to identify the RNAi mechanisms involved in gene silencing, by dsRNAs, in "Drosophila" cells. "Drosophila" S2 cells were transfected with a "lacZ" expression vector to quantify gene expression with β-galactosidase activity. Their results showed co-transfection with "lacZ" dsRNA significantly reduced β-galactosidase activity compared to control dsRNA.
RNA-induced silencing complex | Discovery
Regions of non-coding RNA were mapped in several early experiments examining "S. cerevisiae" using a tiling array approach, which indicated that a large amount of transcriptional activity could be attributed to the intergenic region of the genome. These detected transcripts are not readily observed in the mRNA population because they are rapidly targeted for degradation in both the nucleus and cytoplasm. However, CUTs can be examined in yeast mutants with compromised exosome enzyme capability, which allows for transcripts to accumulate and enables their study and characterization. In 2009, the Steinmetz and Jacquier laboratories performed a series of high-resolution transcriptome maps, further characterizing the widespread distribution and location of non-coding transcripts within eukaryotes.
Cryptic unstable transcript | Discovery and characterization
In 1957 together with Andrey Nikolayevich Belozersky (Андрей Николаевич Белозерский) he conducted comparative analysis of bacterial DNA and RNA, and predicted existence of messenger RNA. He gave the first qualitative description of the structure of high-polymer RNA (1959–61). In 1963 he discovered structural transitions of ribosomes and formulated one of the principles of structure of ribosomes. He discovered artificial ribosomal self-assembly (1963–66). Proposed a molecular mechanism of the ribosome role in protein synthesis (1968). He conducted extra-cellular protein synthesis on modified ribosomes — non-enzymatic translation (together with L.P. Gavrilova) (1970–74). In 1957, he defended his Candidate's Dissertation. In 1962, he defended his doctoral dissertation.
Alexander Spirin | Career
Hurwitz joined the microbiology department at Washington University in 1956 and began investigating the incorporation of ribonucleotides into RNA. Two years later, he moved back to New York and became an Assistant Professor of Microbiology at the New York University (NYU) School of Medicine, where he continued to study RNA synthesis. In 1955, Marianne Grunberg-Manago and Severo Ochoa had reported the isolation of an enzyme that catalyzed the synthesis of RNA. This enzyme was at first hoped to be responsible for the synthesis of RNA in cells, and Ochoa's discovery was honored with a Nobel prize in 1959. However, it was later realized that Ochoa's enzyme did not use DNA to synthesize RNA but instead formed arbitrary sequences, and later this enzyme was found to degrade RNA in cells.
Jerard Hurwitz | Career
Messenger RNA precursors from a wide range of organisms can be edited before being translated into protein. In this process, non-encoded nucleotides may be inserted into specific sites in the RNA, and encoded nucleotides may be removed or replaced. RNA editing was first discovered within the mitochondria of kinetoplastid protozoans, where it has been shown to be extensive. For example, some protein-coding genes encode fewer than 50% of the nucleotides found within the mature, translated mRNA. Other RNA editing events are found in mammals, plants, bacteria and viruses. These latter editing events involve fewer nucleotide modifications, insertions and deletions than the events within kinetoplast DNA, but still have high biological significance for gene expression and its regulation.
History of RNA biology | RNA sequences can be edited within cells
Jerard Hurwitz (November 20, 1928 – January 24, 2019) was an American biochemist who co-discovered RNA polymerase in 1960 along with Sam Weiss, Audrey Stevens, and James Bonner. He most recently worked at the Sloan-Kettering Institute in New York studying DNA replication in eukaryotes and its control.
Jerard Hurwitz | Introduction
Hubert Chantrenne (1918–2007) was a Belgian scientist, and one of the pioneers of molecular biology at the Université Libre de Bruxelles. He elucidated the messenger role played by the ribonucleic acid (RNA) in the synthesis of proteins in ribosome, organelles of the cellular cytoplasm. In 1963, he was awarded the Francqui Prize on Biological and Medical Sciences.
Hubert Chantrenne | Introduction
List of RNA biologists
John Abelson | See also
In 1956, Francis Crick proposed what is now known as the "central dogma" of biology: DNA encodes the genetic information required for an organism to carry out its life cycle. In effect, DNA serves as the "hard drive" which stores genetic data. DNA is replicated and serves as its own template for replication. DNA forms a double helix structure and is a composed of a sugar-phosphate backbone and nitrogenous bases; this can be thought of as a ladder structure where the sides of the ladder are constructed of deoxyribose sugar and phosphate while the rungs of the ladder are composed of paired nitrogenous bases.
Chimeric RNA | Review of RNA Production
Karissa Y. Sanbonmatsu is an American structural biologist at Los Alamos National Laboratory. She works on the mechanism of non-coding RNA complexes including the ribosome, riboswitches, long non-coding RNAs, as well as chromatin. She was the first to perform an atomistic simulation of the ribosome, determine the secondary structure of an intact lncRNA and to publish a one billion atom simulation of a biomolecular complex.
Karissa Sanbonmatsu | Introduction
As noted above, Colin Blake, the author of the Gilbert-Blake theory for the origin of introns and exons, states, “Recent work by Senapathy, when applied to RNA, comprehensively explains the origin of the segregated form of RNA into coding and noncoding regions. It also suggests why a splicing mechanism was developed at the start of primordial evolution.” Senapathy had also proposed a plausible mechanistic and functional rationale why the eukaryotic nucleus originated, a major question in biology. If the transcripts of the split genes and the spliced mRNAs were present in a cell without a nucleus, the ribosomes would try to bind to both the un-spliced primary RNA transcript and the spliced mRNA, which would result in a molecular chaos.
Split gene theory | Origin of the spliceosomal machinery and eukaryotic nucleus
These capacities would have been determined initially by the folded configurations (including those configurations with ribozyme activity) of the RNA replicators that, in turn, would have been encoded in their individual nucleotide sequences.
Natural selection | Origin of life
The lab also studies the dynamic mechanism of RNA splicing, the RNA-binding proteins that determine exonic specificity, and snRNAs that are important regulators of splicing and mRNA maturation.
Gideon Dreyfuss | The Dreyfuss Lab
In 2010, He proposed that RNA modifications could be reversible and may have regulatory roles analogous to well-known reversible DNA and protein modifications. He and colleagues subsequently discovered the first RNA demethylase that oxidatively reverses N6-methyladenosine (mA) methylation in mammalian messenger RNA (mRNA) in 2011. The existence of mA in mRNA was discovered in 1974 in both eukaryotic and viral mRNAs; however, the biological significance and functional role were not known before He’s work. This methylation is the most abundant internal modification in mammalian mRNA. In 2012, two independent studies reported transcriptome-wide mapping of mA in mammalian cells and tissues, revealing a unique distribution pattern.
Chuan He | Research
Hans Kuhn in 1972 laid out a possible process by which the modern genetic system might have arisen from a nucleotide-based precursor, and this led Harold White in 1976 to observe that many of the cofactors essential for enzymatic function are either nucleotides or could have been derived from nucleotides. He proposed that these nucleotide cofactors represent "fossils of nucleic acid enzymes". The phrase "RNA World" was first used by Nobel laureate Walter Gilbert in 1986, in a commentary on how recent observations of the catalytic properties of various forms of RNA fit with this hypothesis.
RNA world | History
The Nirenberg and Matthaei experiment was a scientific experiment performed in May 1961 by Marshall W. Nirenberg and his post-doctoral fellow, J. Heinrich Matthaei at the National Institutes of Health (NIH). The experiment deciphered the first of the 64 triplet codons in the genetic code by using nucleic acid homopolymers to translate specific amino acids. In the experiment, an extract from bacterial cells that could make protein even when no intact living cells were present was prepared. Adding to this extract an artificial form of RNA consisting entirely of uracil-containing nucleotides ("polyuridylic acid" or poly-U), caused it to make a protein composed entirely of the amino acid phenylalanine.
Nirenberg and Matthaei experiment | Introduction
When the human genome project mapped its first chromosome in 1999, it was predicted the genome would contain over 100,000 protein coding genes. However, only around 20,000 were eventually identified. Since then, the advent of bioinformatics approaches combined with genome tiling studies examining the transcriptome, systematic sequencing of full length cDNA libraries and experimental validation (including the creation of miRNA derived antisense oligonucleotides called antagomirs) have revealed that many transcripts are non-protein-coding RNA, including several snoRNAs and miRNAs.
MicroRNA | Non-coding RNAs
Heterochromatin formation, but possibly not maintenance, is dependent on the ribonuclease protein dicer, which is used to generate the initial complement of siRNAs.
RNA-induced transcriptional silencing | Function and mechanisms
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
Non-coding RNAs have been discovered using both experimental and bioinformatic approaches. Bioinformatic approaches can be divided into three main categories. The first involves homology search, although these techniques are by definition unable to find new classes of ncRNAs. The second category includes algorithms designed to discover specific types of ncRNAs that have similar properties. Finally, some discovery methods are based on very general properties of RNA, and are thus able to discover entirely new kinds of ncRNAs.
Bioinformatics discovery of non-coding RNAs | Introduction
In 2007 a study found only one-fifth of transcription across the human genome is associated with protein-coding genes, indicating at least four times more long non-coding than coding RNA sequences. However, it is large-scale complementary DNA (cDNA) sequencing projects such as FANTOM (Functional Annotation of Mammalian cDNA) that reveal the complexity of this transcription. The FANTOM3 project identified ~35,000 non-coding transcripts from ~10,000 distinct loci that bear many signatures of mRNAs, including 5’ capping, splicing, and poly-adenylation, but have little or no open reading frame (ORF). While the abundance of long ncRNAs was unanticipated, this number represents a conservative lower estimate, since it omitted many singleton transcripts and non-polyadenylated transcripts (tiling array data shows more than 40% of transcripts are non-polyadenylated).
Long non-coding RNA | Abundance
snoRNA snR52 was initially discovered using a computational screen of the "Saccharomyces cerevisiae" genome; subsequent work identified Z13 in "Schizosaccharomyces pombe". Further experiments have shown that snR52 is transcribed by RNA polymerase III.
Small nucleolar RNA Z13/snr52 | Introduction
In 1953, James Watson and Francis Crick discovered the double helical structure of the DNA molecule based on the discoveries made by Rosalind Franklin. In 1961, François Jacob and Jacques Monod demonstrated that the products of certain genes regulated the expression of other genes by acting upon specific sites at the edge of those genes. They also hypothesized the existence of an intermediary between DNA and its protein products, which they called messenger RNA. Between 1961 and 1965, the relationship between the information contained in DNA and the structure of proteins was determined: there is a code, the genetic code, which creates a correspondence between the succession of nucleotides in the DNA sequence and a series of amino acids in proteins.
History of molecular biology | General overview
In 1953, Francis Crick, James Watson, Maurice Wilkins and Rosalind Franklin discovered the double helix structure of the DNA macromolecule. Gamow attempted to solve the problem of how the ordering of four different bases (adenine, cytosine, thymine and guanine) in DNA chains might control the synthesis of proteins from their constituent amino acids. Crick has said that Gamow's suggestions helped him in his own thinking about the problem. As related by Crick, Gamow observed that the 4 = 64 possible permutations of the four DNA bases, taken three at a time, would be reduced to 20 distinct combinations if the order was irrelevant..
George Gamow | DNA and RNA
Bartel earned his B.A. degree in Biology from Goshen College in 1982 and his Ph.D. degree in Virology from Harvard University in 1993, under the mentorship of Jack W. Szostak. While in the Szostak lab, Bartel isolated the first ribozymes directly from random sequence, using "in vitro" evolution (among these, the Class I ligase). After he became independent at the Whitehead Institute, he further evolved this ribozyme to function as a RNA-dependent RNA polymerase to extend primers on external RNA templates, bolstering the "RNA world" theory. Bartel later shifted his research focus towards microRNA biology and in particular on understanding their regulatory functions.
David Bartel | Biography
Analysis of mature eukaryotic messenger RNA molecules showed that they are often much smaller than the DNA sequences that encode them. The genes were shown to be discontinuous, composed of sequences that are not present in the final mature RNA (introns), located between sequences that are retained in the mature RNA (exons). Introns were shown to be removed after transcription through a process termed RNA splicing. Splicing of RNA transcripts requires a highly precise and coordinated sequence of molecular events, consisting of (a) definition of boundaries between exons and introns, (b) RNA strand cleavage at exactly those sites, and (c) covalent linking (ligation) of the RNA exons in the correct order.
History of RNA biology | Genes are commonly interrupted by introns that must be removed by RNA splicing
Most recent work has identified that repeat RNA transcripts from the major satellite repeats largely remain chromatin associated and form an RNA-nucleosome scaffold that is supported by RNA:DNA hybrids.
Thomas Jenuwein | Career and research
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