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.
Long non-coding RNAs
RNA
RNA | Long non-coding RNAs
Silencing of blocks of chromatin via recruitment of Polycomb complex so that messenger RNA could not be transcribed from them Many of the newly identified ncRNAs have not been validated for their function. It is also likely that many ncRNAs are non functional. To silence of blocks of chromatin via recruitment of Polycomb complex so that messenger RNA could not be transcribed from them. Many of the conserved, essential and abundant ncRNAs are involved in translation.
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
Non-coding DNA sequences are components of an organism's DNA that do not encode protein sequences. Some non-coding DNA is transcribed into functional non-coding RNA molecules (e.g. transfer RNA, ribosomal RNA, and regulatory RNAs). Other functions of non-coding DNA include the transcriptional and translational regulation of protein-coding sequences, scaffold attachment regions, origins of DNA replication, centromeres and telomeres. Its RNA counterpart is non-coding RNA. The amount of non-coding DNA varies greatly among species. Often, only a small percentage of the genome is responsible for coding proteins, but an increasing percentage is being shown to have regulatory functions. When there is much non-coding DNA, a large proportion appears to have no biological function, as predicted in the 1960s.
Non-coding DNA | Introduction
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
A non-coding RNA (ncRNA) is an RNA molecule that is not translated into a protein. The DNA sequence from which a functional non-coding RNA is transcribed is often called an RNA gene. Abundant and functionally important types of non-coding RNAs include transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs), as well as small RNAs such as microRNAs, siRNAs, piRNAs, snoRNAs, snRNAs, exRNAs, scaRNAs and the long ncRNAs such as Xist and HOTAIR. The number of non-coding RNAs within the human genome is unknown; however, recent transcriptomic and bioinformatic studies suggest that there are thousands of them. Many of the newly identified ncRNAs have not been validated for their function.
Non-coding RNA | Introduction
RNA has many purposes throughout the cell including many important steps in gene expression. Various conformations of the non-Watson-Crick base pairs allow for a multitude of biological functions such as mRNA splicing, siRNA, transport, protein recognition, protein binding, and translation. One example of a biological application of non-canonical base pairs in the kink turn. A kink-turn is found throughout many functional RNA species. It consists of a three-nucleotide bilge which is due to three Hoogsteen base pairs. This kink-turn acts as a marker where various proteins can bind such as the human 15-5k protein or proteins in the L7Ae family.
Non-canonical base pairing | Applications
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
According to the curation of functional mechanisms of lncRNAs based on the literatures, lncRNAs are extensively reported to be involved in transcriptional regulation. A further large-scale sequencing study provides evidence that many transcripts thought to be lncRNAs may, in fact, be translated into proteins.
Long non-coding RNA | Functions
Non-coding RNAs (ncRNA) are RNA molecules that have a function but are not translated into proteins. Small nucleolar RNAs (snoRNAs), one of the largest classes of ncRNA, are further subdivided into the two major C/D and H/ACA snoRNA families. snoRNA serve as guide RNAs for 2'-O-methylation and pseudouridylation of specific nucleotides and indicate the site of modification by direct base pairing with the target RNA. The majority of these snoRNAs are responsible for the post-transcriptional modification of ribosomal RNAs (rRNA) and in some cases of small nuclear RNAs (sRNAs). These post-transcriptional modifications are crucial for rRNA processing, stability and maturation.
Trypanosome H/ACA box snoRNAs | Introduction
Y RNAs are stem loops, necessary for DNA replication through interactions with chromatin and initiation proteins (including the origin recognition complex). They are also components of the Ro60 ribonucleoprotein particle which is a target of autoimmune antibodies in patients with systemic lupus erythematosus.
Non-coding RNA | In DNA replication
Non-coding RNAs (ncRNAs) are RNA transcripts that are not translated into a protein product, but instead exert their function as RNA molecules. They are involved in a range of processes, like post-transcriptional regulation of gene expression, genomic imprinting, and regulating the chromatin state, and thereby the expression, of a given locus. Many ncRNAs have been discovered, but in many cases, their function has yet to be accurately dissected due to technical challenges. ncRNA function is often not affected by introducing point mutations and premature stop codons. ncRNAs are also thought to regulate gene expression, so deletion studies have a hard time distinguishing effects of ncRNA loss from effects of gene misregulation due to the deletion.
CRISPR-Display | Background
In addition to regulating transcription, ncRNAs also control various aspects of post-transcriptional mRNA processing. Similar to small regulatory RNAs such as microRNAs and snoRNAs, these functions often involve complementary base pairing with the target mRNA. The formation of RNA duplexes between complementary ncRNA and mRNA may mask key elements within the mRNA required to bind trans-acting factors, potentially affecting any step in post-transcriptional gene expression including pre-mRNA processing and splicing, transport, translation, and degradation.
Long non-coding RNA | In post-transcriptional regulation
There are also non-coding RNAs involved in gene regulation, RNA processing and other roles. Certain RNAs are able to catalyse chemical reactions such as cutting and ligating other RNA molecules, and the catalysis of peptide bond formation in the ribosome; these are known as ribozymes.
RNA | Overview
Usually, intronic lariats (see above) are debranched and rapidly degraded. However, a debranching failure can lead to the formation of circular intronic long non-coding RNAs, also known as ciRNAs. CiRNA formation, rather than being a random process, seems to depend on the presence of specific elements near the 5' splice site and the branchpoint site (see above). CiRNAs are distinct from circRNAs in that they are prominently found in the nucleus rather than the cytoplasm. In addition, these molecules contain few (if any) miRNA binding sites. Instead of acting as sponges, ciRNAs seem to function in regulating the expression of their parent genes.
Circular RNA | Circular intronic long non-coding RNAs (ciRNAs)
These ncRNAs catalyze their own excision from mRNA, tRNA and rRNA precursors in a wide range of organisms. In mammals it has been found that snoRNAs can also regulate the alternative splicing of mRNA, for example snoRNA HBII-52 regulates the splicing of serotonin receptor 2C.
Non-coding RNA | In RNA splicing
There has been considerable debate about whether lncRNAs have been misannotated and do in fact encode proteins. Several lncRNAs have been found to in fact encode for peptides with biologically significant function. Ribosome profiling studies have suggested that anywhere from 40% to 90% of annotated lncRNAs are in fact translated, although there is disagreement about the correct method for analyzing ribosome profiling data. Additionally, it is thought that many of the peptides produced by lncRNAs may be highly unstable and without biological function.
Long non-coding RNA | Translation
A-to-I editing occurs in a non coding RNA sequences such as introns, untranslated regions (UTRs), LINEs, SINEs (especially Alu repeats). The function of A to I editing in these regions is thought to involve creation of splice sites and retention of RNAs in the nucleus amongst others.
GRIA2 | Type
However, the generation of endo-siRNAs from antisense transcripts or pseudogenes may also silence the expression of their functional counterparts via RISC effector complexes, acting as an important node that integrates various modes of long and short RNA regulation, as exemplified by the Xist and Tsix (see above).
Long non-coding RNA | In siRNA-directed gene regulation
Some non-coding DNA sequences determine where transcription factors attach. A transcription factor is a protein that binds to specific non-coding DNA sequences, thereby controlling the flow (or transcription) of genetic information from DNA to mRNA.
Non-coding DNA | Transcription factors
Messenger RNA (mRNA) is the RNA that carries information from DNA to the ribosome, the sites of protein synthesis (translation) in the cell. The coding sequence of the mRNA determines the amino acid sequence in the protein that is produced. However, many RNAs do not code for protein (about 97% of the transcriptional output is non-protein-coding in eukaryotes). These so-called non-coding RNAs ("ncRNA") can be encoded by their own genes (RNA genes), but can also derive from mRNA introns. The most prominent examples of non-coding RNAs are transfer RNA (tRNA) and ribosomal RNA (rRNA), both of which are involved in the process of translation.
RNA | Overview
Noncoding RNA molecules play many essential roles in cells, especially in the many reactions of protein synthesis and RNA processing. Noncoding RNA include tRNA, ribosomal RNA, microRNA, snRNA and other non-coding RNA genes including about 60,000 long non-coding RNAs (lncRNAs). Although the number of reported lncRNA genes continues to rise and the exact number in the human genome is yet to be defined, many of them are argued to be non-functional. Many ncRNAs are critical elements in gene regulation and expression. Noncoding RNA also contributes to epigenetics, transcription, RNA splicing, and the translational machinery. The role of RNA in genetic regulation and disease offers a new potential level of unexplored genomic complexity.
Human genome | Genes for noncoding RNA (ncRNA)
Long non-coding RNAs (long ncRNAs, lncRNA) are a type of RNA, defined as being transcripts with lengths exceeding 200 nucleotides that are not translated into protein. This somewhat arbitrary limit distinguishes long ncRNAs from small non-coding RNAs such as microRNAs (miRNAs), small interfering RNAs (siRNAs), Piwi-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), and other short RNAs. Long intervening/intergenic noncoding RNAs (lincRNAs) are sequences of lncRNA which do not overlap protein-coding genes.
Long non-coding RNA | Introduction
"Bifunctional RNAs", or "dual-function RNAs", are RNAs that have two distinct functions. The majority of the known bifunctional RNAs are mRNAs that encode both a protein and ncRNAs. However, a growing number of ncRNAs fall into two different ncRNA categories; e.g., H/ACA box snoRNA and miRNA. Two well known examples of bifunctional RNAs are SgrS RNA and RNAIII. However, a handful of other bifunctional RNAs are known to exist (e.g., steroid receptor activator/SRA, VegT RNA, Oskar RNA, ENOD40, p53 RNA and SR1 RNA. Bifunctional RNAs have recently been the subject of a special issue of Biochimie.
Non-coding RNA | Bifunctional RNA
Therefore, editing can also alter protein function. A to I editing occurs in a non coding RNA sequences such as introns, untranslated regions (UTRs), LINEs, SINEs ( especially Alu repeats) The function of A to I editing in these regions is thought to involve creation of splice sites and retention of RNAs in the nucleus amongst others.
5-HT2C receptor | Type
In eukaryotes the spliceosome performs the splicing reactions essential for removing intron sequences, this process is required for the formation of mature mRNA. The spliceosome is another RNP often also known as the snRNP or tri-snRNP. There are two different forms of the spliceosome, the major and minor forms. The ncRNA components of the major spliceosome are U1, U2, U4, U5, and U6. The ncRNA components of the minor spliceosome are U11, U12, U5, U4atac and U6atac. Another group of introns can catalyse their own removal from host transcripts; these are called self-splicing RNAs. There are two main groups of self-splicing RNAs: group I catalytic intron and group II catalytic intron.
Non-coding RNA | In RNA splicing
A typical protein-coding gene is first copied into RNA as an intermediate in the manufacture of the final protein product. In other cases, the RNA molecules are the actual functional products, as in the synthesis of ribosomal RNA and transfer RNA. Some RNAs known as ribozymes are capable of enzymatic function, and microRNA has a regulatory role. The DNA sequences from which such RNAs are transcribed are known as non-coding RNA genes. Some viruses store their entire genomes in the form of RNA, and contain no DNA at all. Because they use RNA to store genes, their cellular hosts may synthesize their proteins as soon as they are infected and without the delay in waiting for transcription.
Gene | RNA genes
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
Therefore, editing can also alter protein function. A to I editing occurs in a noncoding RNA sequences such as introns, untranslated regions (UTRs), LINEs, and SINEs (especially Alu repeats). The function of A to I editing in these regions is thought to involve creation of splice sites and retention of RNAs in the nucleus amongst others.
GRIK2 | Type
Introns are non-coding sections of a gene, transcribed into the precursor mRNA sequence, but ultimately removed by RNA splicing during the processing to mature messenger RNA. Many introns appear to be mobile genetic elements. Studies of group I introns from "Tetrahymena" protozoans indicate that some introns appear to be selfish genetic elements, neutral to the host because they remove themselves from flanking exons during RNA processing and do not produce an expression bias between alleles with and without the intron. Some introns appear to have significant biological function, possibly through ribozyme functionality that may regulate tRNA and rRNA activity as well as protein-coding gene expression, evident in hosts that have become dependent on such introns over long periods of time; for example, the "trnL-intron" is found in all green plants and appears to have been vertically inherited for several billions of years, including more than a billion years within chloroplasts and an additional 2–3 billion years prior in the cyanobacterial ancestors of chloroplasts.
Non-coding DNA | Introns
As with proteins, mutations or imbalances in the ncRNA repertoire within the body can cause a variety of diseases.
Non-coding RNA | Roles in disease
X chromosomes lacking Tsix expression (and thus having high levels of Xist transcription) are inactivated more frequently than normal chromosomes. In drosophilids, which also use an XY sex-determination system, the roX (RNA on the X) RNAs are involved in dosage compensation. Both Xist and roX operate by epigenetic regulation of transcription through the recruitment of histone-modifying enzymes.
Non-coding RNA | Chromosome structure
Brain cytoplasmic 200 long-noncoding RNA (or BC200 lncRNA) is a 200 nucleotide RNA transcript found predominantly in the brain with a primary function of regulating translation by inhibiting its initiation. As a long non-coding RNA, it belongs to a family of RNA transcripts that are not translated into protein (ncRNAs). Of these ncRNAs, lncRNAs are transcripts of 200 nucleotides or longer and are almost three times more prevalent than protein-coding genes. Nevertheless, only a few of the almost 60,000 lncRNAs have been characterized, and little is known about their diverse functions (transcriptional interference, chromatin remodeling, splicing, translation regulation, interaction with miRNAs and siRNAs, and mRNA degradation).
BC200 lncRNA | Introduction
The precise molecular function of "MORT" remains enigmatic; however, it is known that "MORT" is found preferentially in the cell cytoplasm with differential density centrifugation showing that "MORT" is enriched in the 100,000 g fraction, which contains polysomes, microsomes, endoplasmic reticulum, and the plasma membrane. Evidence is mounting that "MORT" acts as a regulator of protein translation through interactions with RNA binding proteins.
MORT (long non-coding RNA) | Cellular Function
A number of ncRNAs are embedded in the 5' UTRs (Untranslated Regions) of protein coding genes and influence their expression in various ways. For example, a riboswitch can directly bind a small target molecule; the binding of the target affects the gene's activity. RNA leader sequences are found upstream of the first gene of amino acid biosynthetic operons. These RNA elements form one of two possible structures in regions encoding very short peptide sequences that are rich in the end product amino acid of the operon. A terminator structure forms when there is an excess of the regulatory amino acid and ribosome movement over the leader transcript is not impeded.
Non-coding RNA | Cis-acting
Telomeres are regions of repetitive DNA at the end of a chromosome, which provide protection from chromosomal deterioration during DNA replication. Recent studies have shown that telomeres function to aid in its own stability. Telomeric repeat-containing RNA (TERRA) are transcripts derived from telomeres. TERRA has been shown to maintain telomerase activity and lengthen the ends of chromosomes.
Non-coding DNA | Telomeres
Some of the most highly conserved noncoding regions are found in the untranslated regions (UTRs) at the 3' end of mature RNA transcripts, rather than in the introns. This suggests an important function operating at the post-transcriptional level. If these regions perform an important regulatory function, the increase in 3'-UTR length over evolutionary time suggests that conserved UTRs contribute to organism complexity. Regulatory motifs in UTRs often conserved in genes belonging to the same metabolic family could potentially be used to develop highly specific medicines that target RNA transcripts.
Conserved non-coding sequence | Untranslated regions
RNA molecules that do not code for any proteins still maintain a function in the cell. The function of the RNA depends on its classification. These roles include: Protein synthesis is aided by functional RNA molecules such as tRNA, which helps add the correct amino acid to a polypeptide chain during translation, rRNA, a major component of ribosomes (which guide protein synthesis), as well as mRNA which carry the instructions for creating the protein product. One type of functional RNA involved in regulation are microRNA (miRNA), which works by repressing translation. These miRNAs work by binding to a complementary target mRNA sequence to prevent translation from occurring.
Gene product | RNA products
In addition to masking key elements within single-stranded RNA, the formation of double-stranded RNA duplexes can also provide a substrate for the generation of endogenous siRNAs (endo-siRNAs) in Drosophila and mouse oocytes. The annealing of complementary sequences, such as antisense or repetitive regions between transcripts, forms an RNA duplex that may be processed by Dicer-2 into endo-siRNAs. Also, long ncRNAs that form extended intramolecular hairpins may be processed into siRNAs, compellingly illustrated by the esi-1 and esi-2 transcripts. Endo-siRNAs generated from these transcripts seem particularly useful in suppressing the spread of mobile transposon elements within the genome in the germline.
Long non-coding RNA | In siRNA-directed gene regulation
Scientists have started to distinguish "functional RNA" ("fRNA") from ncRNA, to describe regions functional at the RNA level that may or may not be stand-alone RNA transcripts. This implies that fRNA (such as riboswitches, SECIS elements, and other cis-regulatory regions) is not ncRNA. Yet fRNA could also include mRNA, as this is RNA coding for protein, and hence is functional. Additionally artificially evolved RNAs also fall under the fRNA umbrella term. Some publications state that "ncRNA" and "fRNA" are nearly synonymous, however others have pointed out that a large proportion of annotated ncRNAs likely have no function. It also has been suggested to simply use the term "RNA", since the distinction from a protein coding RNA (messenger RNA) is already given by the qualifier "mRNA".
Non-coding RNA | Distinction between functional RNA (fRNA) and ncRNA
In accordance with the central dogma of molecular biology, the transcriptome initially encompassed only protein-coding mRNA transcripts. Nevertheless, several RNA subtypes with distinct functions exist. Many RNA transcripts do not code for protein or have different regulatory functions in the process of gene transcription and translation. RNA types which do not fall within the scope of the central dogma of molecular biology are non-coding RNAs which can be divided into two groups of long non-coding RNA and short non-coding RNA. Long non-coding RNA includes all non-coding RNA transcripts that are more than 200 nucleotides long. Members of this group comprise the largest fraction of the non-coding transcriptome.
Transcriptome | Types of RNA transcripts
Large-scale sequencing of cDNA libraries and more recently transcriptomic sequencing by next generation sequencing indicate that long noncoding RNAs number in the order of tens of thousands in mammals. However, despite accumulating evidence suggesting that the majority of these are likely to be functional, only a relatively small proportion has been demonstrated to be biologically relevant. As of January 2016, 294 LncRNAs have been functionally annotated in LncRNAdb (a database of literature described LncRNAs), with the majority of these (183 LncRNAs) being described in humans. As of June 2018, a total of 1867 human lncRNAs that with experimental evidences have been community-curated in LncRNAWiki (a wiki-based, publicly editable and open-content platform for community curation of human lncRNAs) in respect of the functional mechanisms and disease associations, which can also be accessed in LncBook.
Long non-coding RNA | Functions
In higher eukaryotes microRNAs regulate gene expression. A single miRNA can reduce the expression levels of hundreds of genes. The mechanism by which mature miRNA molecules act is through partial complementary to one or more messenger RNA (mRNA) molecules, generally in 3' UTRs. The main function of miRNAs is to down-regulate gene expression. The ncRNA RNase P has also been shown to influence gene expression. In the human nucleus RNase P is required for the normal and efficient transcription of various ncRNAs transcribed by RNA polymerase III. These include tRNA, 5S rRNA, SRP RNA, and U6 snRNA genes. RNase P exerts its role in transcription through association with Pol III and chromatin of active tRNA and 5S rRNA genes.
Non-coding RNA | Trans-acting
This prompted the authors to posit a ‘cogene/gene’ functional regulatory network, showing that one of these ncRNAs, 21A, regulates the expression of its antisense partner gene, CENP-F in trans.
Long non-coding RNA | Transcribed by RNA polymerase III
Long non-coding RNA can associate with DNA in tandem with proteins to alter the rate of gene expression. These RNA are upwards of 200 base pairs. They can be transcribed from a standalone sequence or be part of a promoter, intron or other component of DNA. Long non-coding RNA often complement functional regions of DNA with overlaps or antisense (Kung et al. 2013). To direct transcriptional silencing, a non-coding RNA will associate with a polycomb group protein which to tether it to a specific gene for silencing (Kleinmanns et al. 2014).
Epigenetics of plant growth and development | Long non-coding RNA
Many eukaryotic non-coding RNAs are always polyadenylated at the end of transcription. There are small RNAs where the poly(A) tail is seen only in intermediary forms and not in the mature RNA as the ends are removed during processing, the notable ones being microRNAs. But, for many long noncoding RNAs – a seemingly large group of regulatory RNAs that, for example, includes the RNA Xist, which mediates X chromosome inactivation – a poly(A) tail is part of the mature RNA.
Polyadenylation | Function
This eliminates the ambiguity when addressing a gene "encoding a non-coding" RNA. Besides, there may be a number of ncRNAs that are misannoted in published literature and datasets. (Wayback Machine copy)
Non-coding RNA | Distinction between functional RNA (fRNA) and ncRNA
As nuclear RNA emerges from RNA polymerase, RNA transcripts are immediately covered with RNA-binding proteins that regulate every aspect of RNA metabolism and function including RNA biogenesis, maturation, transport, cellular localization and stability. All RBPs bind RNA, however they do so with different RNA-sequence specificities and affinities, which allows the RBPs to be as diverse as their targets and functions. These targets include mRNA, which codes for proteins, as well as a number of functional non-coding RNAs. NcRNAs almost always function as ribonucleoprotein complexes and not as naked RNAs. These non-coding RNAs include microRNAs, small interfering RNAs (siRNA), as well as splicesomal small nuclear RNAs (snRNA).
RNA-binding protein | Diversity
Transcriptomics is most commonly applied to the mRNA content of the cell. However, the same techniques are equally applicable to non-coding RNAs (ncRNAs) that are not translated into a protein, but instead have direct functions (e.g. roles in protein translation, DNA replication, RNA splicing, and transcriptional regulation). Many of these ncRNAs affect disease states, including cancer, cardiovascular, and neurological diseases.
Transcriptomics technologies | Non-coding RNA
Thus, this novel noncoding RNA appears to have an important structural role in the nuclear paraspeckles. There are two isoforms of NEAT1, NEAT1_1 and NEAT1_2, which are regulated by alternative 3′-end processing. Mutant mice lacking Neat1 do not exhibit overt external abnormalities, but the female mice exhibit decreased fertility and lactation defect.
NEAT1 | Introduction
Telomeres form the terminal region of mammalian chromosomes and are essential for stability and aging and play central roles in diseases such as cancer. Telomeres have been long considered transcriptionally inert DNA-protein complexes until it was shown in the late 2000s that telomeric repeats may be transcribed as telomeric RNAs (TelRNAs) or telomeric repeat-containing RNAs. These ncRNAs are heterogeneous in length, transcribed from several sub-telomeric loci and physically localise to telomeres. Their association with chromatin, which suggests an involvement in regulating telomere specific heterochromatin modifications, is repressed by SMG proteins that protect chromosome ends from telomere loss. In addition, TelRNAs block telomerase activity in vitro and may therefore regulate telomerase activity.
Long non-coding RNA | Telomeric non-coding RNAs
The study of the reversibility of these modifications is an active area of research. These modifications impact a variety of different qualities including the lncRNA's function and the initiation of translation. Modifications to lncRNAs have been demonstrated to impact where they localize within the cell and while complicated structures, such as the crucifix of tRNA, are not typically found in lncRNA, modifications may alter their structure and impact the overall function and pathway the lncRNA takes.
Epitranscriptome | Long non-coding RNA (lncRNA)
Some non-coding DNA sequences determine the expression levels of various genes, both those that are transcribed to proteins and those that themselves are involved in gene regulation.
Non-coding DNA | Regulating gene expression
Secondary and three-dimensional structures of RNA are formed and stabilized through non-canonical base pairs. Base pairs make up many secondary structural blocks which aid the folding of RNA complexes and three dimensional structures. The overall folded RNA is stabilized by the tertiary and secondary structures canonically base pairing together. Due to the many non-canonical base pairs there are an unlimited amount of structures which allow for the diverse functions of RNA. The arrangement of the non-canonical bases allow long-range RNA interactions, recognition of proteins and other molecules, and structural stabilizing elements. Many of the common non-canonical base pairs can be added to a stacked RNA stem without disturbing its helical character.
Non-canonical base pairing | 3-D Structure
Like DNA, most biologically active RNAs, including mRNA, tRNA, rRNA, snRNAs, and other non-coding RNAs, contain self-complementary sequences that allow parts of the RNA to fold and pair with itself to form double helices. Analysis of these RNAs has revealed that 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. In this fashion, RNAs can achieve chemical catalysis (like enzymes). For instance, determination of the structure of the ribosome—an RNA-protein complex that catalyzes peptide bond formation—revealed that its active site is composed entirely of RNA.
RNA | Comparison with DNA
Instead, it functions in rRNA processing by directing pre-rRNA cleavage.
Small nucleolar RNA | C/D box
These two loosely structured domains may even be concatenated to other ncRNAs such as B1 elements to impart their repressive role. The abundance and distribution of Alu elements and similar repetitive elements throughout the mammalian genome may be partly due to these functional domains being co-opted into other long ncRNAs during evolution, with the presence of functional repeat sequence domains being a common characteristic of several known long ncRNAs including Kcnq1ot1, Xlsirt and Xist.
Long non-coding RNA | Regulating basal transcription machinery
Initial studies into lncRNA conservation noted that as a class, they were enriched for conserved sequence elements, depleted in substitution and insertion/deletion rates and depleted in rare frequency variants, indicative of purifying selection maintaining lncRNA function. However, further investigations into vertebrate lncRNAs revealed that while lncRNAs are conserved in sequence, they are not conserved in transcription. In other words, even when the sequence of a human lncRNA is conserved in another vertebrate species, there is often no transcription of a lncRNA in the orthologous genomic region. Some argue that these observations suggest non-functionality of the majority of lncRNAs, while others argue that they may be indicative of rapid species-specific adaptive selection.
Long non-coding RNA | Conservation
The role of the Paraspeckle is as of yet not fully understood. It has been suggested that the activity of NONO (a.k.a p54nrb), a protein component, is dependent on its localisation within the nucleus. Thus, one explanation of the Paraspeckle’s function is that it provides ordered localisation of its component proteins and to thereby help direct their activity. In turn, this is believed to give the Paraspeckle a regulatory function over transcription. Also, a meta-analysis by Fox et.al. (2018) links the Paraspeckle’s regulation to its ability to sequester or steal component proteins and RNAs. This causes other nuclear compartments to be depleted.
Paraspeckle | Function
Although early, these studies suggest an involvement for telomeric ncRNAs in various aspects of telomere biology.
Long non-coding RNA | Telomeric non-coding RNAs
Many of the conserved, essential and abundant ncRNAs are involved in translation. Ribonucleoprotein (RNP) particles called ribosomes are the 'factories' where translation takes place in the cell. The ribosome consists of more than 60% ribosomal RNA; these are made up of 3 ncRNAs in prokaryotes and 4 ncRNAs in eukaryotes. Ribosomal RNAs catalyse the translation of nucleotide sequences to protein. Another set of ncRNAs, Transfer RNAs, form an 'adaptor molecule' between mRNA and protein. The H/ACA box and C/D box snoRNAs are ncRNAs found in archaea and eukaryotes. RNase MRP is restricted to eukaryotes. Both groups of ncRNA are involved in the maturation of rRNA.
Non-coding RNA | In translation
These elements are transcribed as ncRNAs by RNAP III in response to environmental stresses such as heat shock, where they then bind to RNAP II with high affinity and prevent the formation of active pre-initiation complexes. This allows for the broad and rapid repression of gene expression in response to stress. A dissection of the functional sequences within Alu RNA transcripts has drafted a modular structure analogous to the organization of domains in protein transcription factors. The Alu RNA contains two ‘arms’, each of which may bind one RNAP II molecule, as well as two regulatory domains that are responsible for RNAP II transcriptional repression in vitro.
Long non-coding RNA | Regulating basal transcription machinery
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
It has been shown that 7SK RNA, a metazoan ncRNA, acts as a negative regulator of the RNA polymerase II elongation factor P-TEFb, and that this activity is influenced by stress response pathways.
Non-coding RNA | Trans-acting
The snoRNAs guide covalent modifications of rRNA, tRNA and snRNAs; RNase MRP cleaves the internal transcribed spacer 1 between 18S and 5.8S rRNAs. The ubiquitous ncRNA, RNase P, is an evolutionary relative of RNase MRP. RNase P matures tRNA sequences by generating mature 5'-ends of tRNAs through cleaving the 5'-leader elements of precursor-tRNAs. Another ubiquitous RNP called SRP recognizes and transports specific nascent proteins to the endoplasmic reticulum in eukaryotes and the plasma membrane in prokaryotes. In bacteria Transfer-messenger RNA (tmRNA) is an RNP involved in rescuing stalled ribosomes, tagging incomplete polypeptides and promoting the degradation of aberrant mRNA.
Non-coding RNA | In translation
The non-structural proteins function in viral replication and assembly. These proteins are named NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5, and NS2K, where NS denotes “non-structural”. NS3 has enzymatic activity as a helicase and protease, while NS5 is an RNA dependent RNA polymerase, allowing the virus to replicate a new (+)RNA genome by creating a complementary (-)RNA strand and using that as a template for the genome. The other non-structural proteins function in RNA replication, viral assembly and release, processing the viral polyprotein and inhibiting the host’s innate immunity, like inhibiting interferon signaling.
Sepik virus | Replication and transcription
In addition, several defined suites of non-Watson-Crick base pairs assemble into RNA modules that form recurrent, rather regular, building blocks of the tertiary architecture of folded RNAs. RNA modules are intrinsic to RNA architecture are therefore disconnected from a biological function specifically attached to a RNA sequence. RNA modules occur in all kingdoms of life and in structured RNAs with diverse functions. Because of chemical and geometrical constraints, isostericity between non-Watson-Crick pairs is restricted and this leads to higher sequence conservation with coevolution (neutral networks) in RNA modules with, consequently, greater difficulties in extracting 3D information from sequence analysis.
Eric Westhof | Nucleic acid base pairs
Piwi-interacting RNAs (piRNAs) expressed in mammalian testes and somatic cells form RNA-protein complexes with Piwi proteins. These piRNA complexes (piRCs) have been linked to transcriptional gene silencing of retrotransposons and other genetic elements in germ line cells, particularly those in spermatogenesis. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) are repeats found in the DNA of many bacteria and archaea. The repeats are separated by spacers of similar length. It has been demonstrated that these spacers can be derived from phage and subsequently help protect the cell from infection.
Non-coding RNA | In genome defense
In molecular biology, non-protein coding RNA, upstream of F2R/PAR1, also known as NCRUPAR is a long non-coding RNA. It is located upstream of the PAR-1 gene and upregulates PAR-1 expression.
NCRUPAR | Introduction
The One or Two Kilobases Of Non-Coding RNA motif (OTKONC RNA motif) describes a conserved RNA structure that was discovered by bioinformatics. OTKONC motif RNAs have not yet (as of 2018) been found in a classified organism, but are known only in metagenomic sequences. OTKONC are so-named because they exist between regions of 1–2 kilobases of sequence that are not predicted to contain any protein-coding genes. Such large non-coding regions are uncommon in bacteria, and it is likely that OTKONC RNAs are present in bacteria in view of protein-coding genes that reside farther away from the RNAs. OTKONC RNAs presumably function in "trans" as small RNAs, and it is unknown what, if anything, their function has to do with the surrounding non-coding regions.
OTKONC RNA motif | Introduction
Small RNAs are noncoding RNA molecules between 20 and 200 nucleotide in length, which are contained in the bigger class of ncRNAs. In particular, the term “small” refers to bacteria, while for eukaryotic cells the more general term “ncRNA” is used.. These molecules are characterized by the presence of a high density of STOP codons and very short ORF sequences: for this reason, they are not involved in coding, but they act as regulators of gene expression in the cell. Small RNAs include several different classes of noncoding RNAs, depending on their sizes and functions: snRNA, snoRNA, scRNA, piRNA, miRNA and siRNA.
Small RNA sequencing | Introduction
Non-coding sequences important for gene regulation, such as the binding or recognition sites of ribosomes and transcription factors, may be conserved within a genome. For example, the promoter of a conserved gene or operon may also be conserved. As with proteins, nucleic acids that are important for the structure and function of non-coding RNA (ncRNA) can also be conserved. However, sequence conservation in ncRNAs is generally poor compared to protein-coding sequences, and base pairs that contribute to structure or function are often conserved instead.
Conserved sequence | Non-coding
RNA4 (1,998 base pairs) encodes for the major nonstructural protein and another minor nonstructural protein, NS4. RNA2-RNA4 use an ambisense coding strategy, meaning those RNA segments contain both negative sense and positive sense sections, in order to code for two proteins.
Rice hoja blanca tenuivirus | Genome
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
fumigatus" are conserved across other strains of fungus. This study also identified several partial tRNA sequences within the cDNA libraries which corresponded to either the 5’ or 3’ halves of tRNA molecules. These partial tRNAs are thought to have been created by enonuclolytic cleavage within the anti-codon loop. It has been suggested that these partial tRNA stall protein synthesis however, further studies are required to determine their exact function. The table below summarised the type, genome location and corresponding target sites of the ncRNAs identified in "A. fumigatus". Non-Coding RNAs present in " A. fumigatus"
Aspergillus fumigatus non-coding RNAs | Introduction
Some non-coding DNA sequences must have some important biological function. This is indicated by comparative genomics studies that report highly conserved regions of non-coding DNA, sometimes on time-scales of hundreds of millions of years. This implies that these non-coding regions are under strong evolutionary pressure and positive selection. For example, in the genomes of humans and mice, which diverged from a common ancestor 65–75 million years ago, protein-coding DNA sequences account for only about 20% of conserved DNA, with the remaining 80% of conserved DNA represented in non-coding regions. Linkage mapping often identifies chromosomal regions associated with a disease with no evidence of functional coding variants of genes within the region, suggesting that disease-causing genetic variants lie in the non-coding DNA.
Non-coding DNA | Evidence of functionality
In most organisms non-coding genes (ncRNA) are transcribed as precursors that undergo further processing. In the case of ribosomal RNAs (rRNA), they are often transcribed as a pre-rRNA that contains one or more rRNAs. The pre-rRNA is cleaved and modified (2′-O-methylation and pseudouridine formation) at specific sites by approximately 150 different small nucleolus-restricted RNA species, called snoRNAs. SnoRNAs associate with proteins, forming snoRNPs. While snoRNA part basepair with the target RNA and thus position the modification at a precise site, the protein part performs the catalytical reaction. In eukaryotes, in particular a snoRNP called RNase, MRP cleaves the 45S pre-rRNA into the 28S, 5.8S, and 18S rRNAs.
Gene expression | Non-coding RNA maturation
Long non-coding RNAs, or lncRNAs, are RNA transcripts produced by RNA polymerase II that are not translated but participate in the regulation of gene expression. Long non-coding RNAs are used in various epigenetic processes in development, including the regulation of Hox genes, as well as in the creation of Barr bodies.
Epigenetics of human development | Role of lncRNAs
This information is replicated as and when the two strands separate. A large part of DNA (more than 98% for humans) is non-coding, meaning that these sections do not serve as patterns for protein sequences. The two strands of DNA run in opposite directions to each other and are thus antiparallel. Attached to each sugar is one of four types of nucleobases (informally, "bases"). It is the sequence of these four nucleobases along the backbone that encodes genetic information. RNA strands are created using DNA strands as a template in a process called transcription, where DNA bases are exchanged for their corresponding bases except in the case of thymine (T), for which RNA substitutes uracil (U).
DNA | Introduction
Recent findings also reveal that RNase P has a new function. It has been shown that human nuclear RNase P is required for the normal and efficient transcription of various small noncoding RNAs, such as tRNA, 5S rRNA, SRP RNA and U6 snRNA genes, which are transcribed by RNA polymerase III, one of three major nuclear RNA polymerases in human cells.
Ribonuclease P | 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
A microRNA (abbreviated miRNA) is a small non-coding RNA molecule (containing about 22 nucleotides) found in plants, animals and some viruses, that functions in RNA silencing and post-transcriptional regulation of gene expression. miRNAs function via base-pairing with complementary sequences within mRNA molecules. As a result, these mRNA molecules are silenced, by one or more of the following processes: (1) Cleavage of the mRNA strand into two pieces, (2) Destabilization of the mRNA through shortening of its poly(A) tail, and (3) Less efficient translation of the mRNA into proteins by ribosomes. miRNAs resemble the small interfering RNAs (siRNAs) of the RNA interference (RNAi) pathway, except miRNAs derive from regions of RNA transcripts that fold back on themselves to form short hairpins, whereas siRNAs derive from longer regions of double-stranded RNA.
MicroRNA | Introduction
Basic secondary structural elements of RNA include bulges, double helices, hairpin loops and internal loops. An example of a hairpin loop of RNA is given in Figure 7. As shown in the figure hairpin loops and internal loops require a sudden change in backbone direction. Non-canonical base pairing allows for increased flexibility at junctions or turns in the secondary structure.
Non-canonical base pairing | Secondary
Many ncRNAs show abnormal expression patterns in cancerous tissues. These include miRNAs, long mRNA-like ncRNAs, GAS5, SNORD50, telomerase RNA and Y RNAs. The miRNAs are involved in the large scale regulation of many protein coding genes, the Y RNAs are important for the initiation of DNA replication, telomerase RNA that serves as a primer for telomerase, an RNP that extends telomeric regions at chromosome ends (see telomeres and disease for more information). The direct function of the long mRNA-like ncRNAs is less clear. Germ-line mutations in miR-16-1 and miR-15 primary precursors have been shown to be much more frequent in patients with chronic lymphocytic leukemia compared to control populations.
Non-coding RNA | Cancer
Even snRNAs and snoRNAs themselves undergo series of modification before they become part of functional RNP complex. This is done either in the nucleoplasm or in the specialized compartments called Cajal bodies. Their bases are methylated or pseudouridinilated by a group of small Cajal body-specific RNAs (scaRNAs), which are structurally similar to snoRNAs.
Gene expression | Non-coding RNA maturation
This is especially true for non-coding RNA (see below). The number of protein-coding genes is better known but there are still on the order of 1,400 questionable genes which may or may not encode functional proteins, usually encoded by short open reading frames. Table 2 gives estimates from various projects and shows these discrepancies.
Human genome | Molecular organization and gene content
U6 snRNA is the non-coding small nuclear RNA (snRNA) component of U6 snRNP ("small nuclear ribonucleoprotein"), an RNA-protein complex that combines with other snRNPs, unmodified pre-mRNA, and various other proteins to assemble a spliceosome, a large RNA-protein molecular complex that catalyzes the excision of introns from pre-mRNA. Splicing, or the removal of introns, is a major aspect of post-transcriptional modification and takes place only in the nucleus of eukaryotes. The RNA sequence of U6 is the most highly conserved across species of all five of the snRNAs involved in the spliceosome, suggesting that the function of the U6 snRNA has remained both crucial and unchanged through evolution.
U6 spliceosomal RNA | Introduction
For example, a relatively abundant ciRNA called ci-ankrd52 positively regulates Pol II transcription. Many ciRNAs remain at their "sites of synthesis" in the nucleus. However, ciRNA may have roles other than simply regulating their parent genes, as ciRNAs do localize to additional sites in the nucleus other than their "sites of synthesis".
Circular RNA | Circular intronic long non-coding RNAs (ciRNAs)
This is a list of long noncoding RNA databases, which provide information about lncRNAs.
List of long non-coding RNA databases | Introduction
Because of the question of the "Salmonella" sequences, some ambiguity remains as to whether or not "nuoG" RNAs do, in fact, function as structured RNAs.
NuoG RNA motif | Introduction
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
When there is a deficiency of the charged tRNA of the regulatory amino acid the ribosome translating the leader peptide stalls and the antiterminator structure forms. This allows RNA polymerase to transcribe the operon. Known RNA leaders are Histidine operon leader, Leucine operon leader, Threonine operon leader and the Tryptophan operon leader. Iron response elements (IRE) are bound by iron response proteins (IRP). The IRE is found in UTRs of various mRNAs whose products are involved in iron metabolism. When iron concentration is low, IRPs bind the ferritin mRNA IRE leading to translation repression.
Non-coding RNA | Cis-acting
Two functions have been described for Y RNAs in the literature: As a repressor of Ro60, and as an initiation factor for DNA replication. Mutant human Y RNAs lacking the conserved binding site for Ro60 protein still support DNA replication, indicating that binding to Ro protein and promoting DNA replication are two separable functions of Y RNAs. Although Y RNA-derived small RNAs are similar in size to microRNAs, it has been shown that these Y RNA fragments are not involved in the microRNA pathway.
Y RNA | Function
In eukaryotes, RNA transcription is a tightly regulated process. NcRNAs can target different aspects of this process, targeting transcriptional activators or repressors, different components of the transcription reaction including RNA polymerase (RNAP) II and even the DNA duplex to regulate gene transcription and expression. In combination these ncRNAs may comprise a regulatory network that, including transcription factors, finely control gene expression in complex eukaryotes. NcRNAs modulate the function of transcription factors by several different mechanisms, including functioning themselves as co-regulators, modifying transcription factor activity, or regulating the association and activity of co-regulators. For example, the ncRNA Evf-2 functions as a co-activator for the homeobox transcription factor Dlx2, which plays important roles in forebrain development and neurogenesis.
Long non-coding RNA | In gene-specific transcription
Three-dimensional structures are formed through the long-range intra-molecular interactions between the secondary structures. This leads to the formation of pseudoknots, ribose zippers, kissing hairpin loops, or co-axial pseudocontinuous helices. The three-dimensional structures of RNA are primarily determined through molecular simulations or computationally guided measurements. An example of a Pseudoknot is given in Figure 8.
Non-canonical base pairing | Tertiary
The rRNA and RNA processing factors form large aggregates called the nucleolus. In the case of transfer RNA (tRNA), for example, the 5′ sequence is removed by RNase P, whereas the 3′ end is removed by the tRNase Z enzyme and the non-templated 3′ CCA tail is added by a nucleotidyl transferase. In the case of micro RNA (miRNA), miRNAs are first transcribed as primary transcripts or pri-miRNA with a cap and poly-A tail and processed to short, 70-nucleotide stem-loop structures known as pre-miRNA in the cell nucleus by the enzymes Drosha and Pasha. After being exported, it is then processed to mature miRNAs in the cytoplasm by interaction with the endonuclease Dicer, which also initiates the formation of the RNA-induced silencing complex (RISC), composed of the Argonaute protein.
Gene expression | Non-coding RNA maturation
The ribonucleoproteins play a role of protection. mRNAs never occur as free RNA molecules in the cell. They always associate with ribonucleoproteins and function as ribonucleoprotein complexes. In the same way, the genomes of negative-strand RNA viruses never exist as free RNA molecule. The ribonucleoproteins protect their genomes from RNase. Nucleoproteins are often the major antigens for viruses because they have strain-specific and group-specific antigenic determinants.
Nucleoprotein | Functions
BRAF-activated non-protein coding RNA is a protein that in humans is encoded by the BANCR gene.
Braf-activated non-protein coding rna | Introduction
NONO is involved with many nuclear processes and binds to both DNA and RNA. As with all proteins of the DBHS familprotein is described as a multifunctional nuclear protein. The NONO protein has been shown to be implicated in many biological functions including, pre-mRNA splicing; activation of transcription; termination of transcription; DNA unwinding and pairing and maintaining correct circadian clock function. NONO has been identified to bind with Rasd1 protein, in resulting dimer Rasd1 may act to modulate the function of NONO to down regulate the expression of the CREB genes, NR4A1 and Nr4A2.
Non-POU domain-containing octamer-binding protein | Functions
Eukaryotic transcription proceeds in three sequential stages: initiation, elongation, and termination. The RNAs transcribed serve diverse functions. For example, structural components of the ribosome are transcribed by RNA polymerase I. Protein coding genes are transcribed by RNA polymerase II into messenger RNAs (mRNAs) that carry the information from DNA to the site of protein synthesis. More abundantly made are the so-called non-coding RNAs account for the large majority of the transcriptional output of a cell. These non-coding RNAs perform a variety of important cellular functions.
Eukaryotic transcription | Introduction
In molecular biology, Cyanobacterial non-coding RNAs are non-coding RNAs which have been identified in species of cyanobacteria. Large scale screens have identified 21 Yfr (cYanobacterial functional RNAs) in the marine cyanobacterium "Prochlorococcus" and related species such as "Synechococcus". These include the Yfr1 and Yfr2 RNAs. In "Prochlorococcus" and "Synechocystis", non-coding RNAs have been shown to regulate gene expression. NsiR4, widely conserved throughout the cyanobacterial phylum, has been shown to be involved in nitrogen assimilation control in Synechocystis sp. PCC 6803 and in the filamentous, nitrogen-fixing Anabaena sp. PCC 7120. PsrR1 (photosynthesis regulatory RNA1), formerly known as Syr1 discovered in "Synechocystis sp PCC 6803," is a regulatory factor controlling photosynthetic functions.
Cyanobacterial non-coding RNA | Introduction
An operator is a segment of DNA to which a repressor binds. A repressor is a DNA-binding protein that regulates the expression of one or more genes by binding to the operator and blocking the attachment of RNA polymerase to the promoter, thus preventing transcription of the genes. This blocking of expression is called repression.
Non-coding DNA | Operators
The presence of allele-specific histone methylation at the Igf2r locus suggests Air also mediates silencing via chromatin modification.
Long non-coding RNA | Imprinting