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71-583: 7503 213742 ENSG00000229807 ENSMUSG00000086503 n a n/a n/a n/a n/a n/a Xist (X-inactive specific transcript) is a non-coding RNA transcribed from the X chromosome of the placental mammals that acts as a major effector of the X-inactivation process. It is a component of the Xic – X-chromosome inactivation centre – along with two other RNA genes ( Jpx and Ftx ) and two protein genes ( Tsx and Cnbp2 ). The Xist RNA,

142-595: 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. The bacterial ncRNA, 6S RNA , specifically associates with RNA polymerase holoenzyme containing the sigma70 specificity factor. This interaction represses expression from a sigma70-dependent promoter during stationary phase . Another bacterial ncRNA, OxyS RNA represses translation by binding to Shine-Dalgarno sequences thereby occluding ribosome binding. OxyS RNA

213-418: 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

284-414: A substrate for enzymatic reactions . The formation of a stem-loop is dependent on the stability of the helix and loop regions. The first prerequisite is the presence of a sequence that can fold back on itself to form a paired double helix. The stability of this helix is determined by its length, the number of mismatches or bulges it contains (a small number are tolerable, especially in a long helix), and

355-559: A duplication of the SNORD115 cluster displays autistic-like behaviour. A recent small study of post-mortem brain tissue demonstrated altered expression of long non-coding RNAs in the prefrontal cortex and cerebellum of autistic brains as compared to controls. Mutations within RNase MRP have been shown to cause cartilage–hair hypoplasia , a disease associated with an array of symptoms such as short stature, sparse hair, skeletal abnormalities and

426-408: 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. Many of the conserved, essential and abundant ncRNAs are involved in translation . Ribonucleoprotein (RNP) particles called ribosomes are

497-480: 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 140 kg of commercial baker's yeast to give just 1 g of purified tRNA for analysis. The 80 nucleotide tRNA

568-411: A large (17 kb in humans) transcript, is expressed on the inactive chromosome and not on the active one. It is processed in a similar way to mRNAs , through splicing and polyadenylation . However, it remains untranslated . It has been suggested that this RNA gene evolved at least partly from a protein-coding gene that became a pseudogene . The inactive X chromosome is coated with this transcript, which

639-682: 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 . 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. Stem-loop Stem-loops are nucleic acid secondary structural elements which form via intramolecular base pairing in single-stranded DNA or RNA . They are also referred to as hairpins or hairpin loops. A stem-loop occurs when two regions of

710-502: A rare SNP ( rs11614913 ) that overlaps hsa-mir-196a-2 has been found to be associated with non-small cell lung carcinoma . Likewise, a screen of 17 miRNAs that have been predicted to regulate a number of breast cancer associated genes found variations in the microRNAs miR-17 and miR-30c-1of patients; these patients were noncarriers of BRCA1 or BRCA2 mutations, lending the possibility that familial breast cancer may be caused by variation in these miRNAs. The p53 tumor suppressor

781-410: A revision of the repA structure model that includes both intra-repeat and inter-repeat folding found in previous models as well as novel features (see Figure). In addition to its agreement with the in vivo data, this revised model is highly conserved in rodents and mammals (including humans) suggesting functional importance for repA structure. Although the exact function of the repA region is uncertain, it

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852-527: A single 19-bp antisense cell-permeating PNA targeted against a particular region of Xist RNA prevented the formation of Xi and inhibited cis-silencing of X-linked genes. The association of the Xi with macro-histone H2A is also disturbed by PNA interference mapping. The X-inactivation process occurs in mice even in the absence of this gene via epigenetic regulation , but Xist is required to stabilize this silencing. In addition to being expressed in nearly all females, XIST

923-433: A single non-coding RNA of a bacterial pathogen . As with proteins , mutations or imbalances in the ncRNA repertoire within the body can cause a variety of diseases. 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,

994-495: A suppressed immune system that is frequent among Amish and Finnish . The best characterised variant is an A-to-G transition at nucleotide 70 that is in a loop region two bases 5' of a conserved pseudoknot . However, many other mutations within RNase MRP also cause CHH. The antisense RNA, BACE1-AS is transcribed from the opposite strand to BACE1 and is upregulated in patients with Alzheimer's disease . BACE1-AS regulates

1065-505: Is a crucial regulator of estrogen -receptor-alpha. Non-coding RNAs are crucial in the development of several endocrine organs, as well as in endocrine diseases such as diabetes mellitus . Specifically in the MCF-7 cell line, addition of 17β- estradiol increased global transcription of the noncoding RNAs called lncRNAs near estrogen-activated coding genes. C. elegans was shown to learn and inherit pathogenic avoidance after exposure to

1136-603: Is a negative regulator of Xist. 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 . Bifunctional RNAs , or dual-function RNAs , are RNAs that have two distinct functions. The majority of

1207-461: Is a target of autoimmune antibodies in patients with systemic lupus erythematosus . The expression of many thousands of genes are regulated by ncRNAs. This regulation can occur in trans or in cis . There is increasing evidence that a special type of ncRNAs called enhancer RNAs , transcribed from the enhancer region of a gene, act to promote gene expression. In higher eukaryotes microRNAs regulate gene expression. A single miRNA can reduce

1278-498: Is a transcript of the Xist gene at the XIC center. The Tsix antisense transcript acts in cis to repress the transcription of Xist, which negatively regulates its expression. The mechanism behind how Tsix modulates Xist activity in cis is poorly understood; however, there are a few theories on its mechanism. One theory is that Tsix is involved in chromatin modification at the Xist locus and another

1349-430: Is an excess of the regulatory amino acid and ribosome movement over the leader transcript is not impeded. 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

1420-463: Is arguably the most important agent in preventing tumor formation and progression. The p53 protein functions as a transcription factor with a crucial role in orchestrating the cellular stress response. In addition to its crucial role in cancer, p53 has been implicated in other diseases including diabetes, cell death after ischemia, and various neurodegenerative diseases such as Huntington, Parkinson, and Alzheimer. Studies have suggested that p53 expression

1491-473: Is essential for the inactivation. X chromosomes lacking Xist will not be inactivated, while duplication of the Xist gene on another chromosome causes inactivation of that chromosome. The human Xist gene was discovered by Andrea Ballabio through a cDNA library screening and then characterized in collaboration with Carolyn J. Brown and Hunt Willard . X-inactivation is an early developmental process in mammalian females that transcriptionally silences one of

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1562-461: Is expressed in narrow developmental contexts in males including human preimplantation embryos, primordial germ cells, testicular germ cell tumors, and a subset of male cancers of diverse lineages. It may be involved in the dosage compensation of supernumerary X chromosomes in the latter two cases. The human Xist RNA gene is located on the long (q) arm of the X chromosome. The Xist RNA gene contains conserved repeats within its structure. Its gene product

1633-468: Is induced in response to oxidative stress in Escherichia coli. The B2 RNA is a small noncoding RNA polymerase III transcript that represses mRNA transcription in response to heat shock in mouse cells. B2 RNA inhibits transcription by binding to core Pol II. Through this interaction, B2 RNA assembles into preinitiation complexes at the promoter and blocks RNA synthesis. A recent study has shown that just

1704-453: Is largely localized in the nucleus. The Xist RNA gene features a conserved A region, which contains 8 repeats separated by U-rich spacers. The A region appears to encode two long stem-loop RNA structures that each include four repeats. An ortholog of the Xist RNA gene in humans has been identified in mice. This ortholog encodes a 15 kb Xist transcript that is also localized in the nucleus. However,

1775-457: Is maintained in epiblast, an X is inactivated and the Xist allele is turned off in the active X chromosome. In maturing XX primordial germ cells, Xist is downregulated and X reactivation occurs once again. Mutations in the XIST promoter cause familial skewed X-inactivation . XIST has been shown to interact with BRCA1 . Non-coding RNA The number of non-coding RNAs within the human genome

1846-411: Is proposed that Nanog and Oct4 are involved in the repression of Xist expression. Polycomb repressive complex 2 ( PRC2 ) consist of a class of polycomb group proteins that are involved in catalyzing the trimethylation of histone H3 on lysine 27 (K27), which results in chromatin repression, and thus leads to transcriptional silencing. Xist RNA recruits polycomb complexes to the inactive X chromosome at

1917-403: Is restricted to eukaryotes. Both groups of ncRNA are involved in the maturation of rRNA. 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

1988-459: Is still poorly understood. If one of the X chromosomes is not inactivated or is partially expressed, it could lead to over expression of the X chromosome and it could be lethal in some cases. Turner's Syndrome is one example of where dosage compensation does not equally express the X chromosome, and in females one of the X chromosomes is missing or has abnormalities, which leads to physical abnormalities and also gonadal dysfunction in females due to

2059-521: Is subject to regulation by non-coding RNA. Another example of non-coding RNA dysregulated in cancer cells is the long non-coding RNA Linc00707. Linc00707 is upregulated and sponges miRNAs in human bone marrow-derived mesenchymal stem cells, gastric cancer or breast cancer, and thus promotes osteogenesis, contributes to hepatocellular carcinoma progression, promotes proliferation and metastasis, or indirectly regulates expression of proteins involved in cancer aggressiveness, respectively. The deletion of

2130-477: Is that transcription factors of pluripotent cells play a role in Xist repression. The Tsix antisense is believed to activate DNA methyl transferases that methylate the Xist promoter , in return resulting in inhibition of the Xist promoter and thus the expression of the Xist gene. Methylation of histone 3 lysine 4 (H3K4) produces an active chromatin structure, which recruits transcription factors and thus allows for transcription to occur, therefore in this case

2201-642: Is unknown; however, recent transcriptomic and bioinformatic studies suggest that there are thousands of non-coding transcripts. Many of the newly identified ncRNAs have unknown functions, if any. There is no consensus on how much of non-coding transcription is functional: some believe most ncRNAs to be non-functional "junk RNA", spurious transcriptions, while others expect that many non-coding transcripts have functions to be discovered. 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

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2272-444: The 5'UTR of prokaryotes. These structures are often bound by proteins or cause the attenuation of a transcript in order to regulate translation. The mRNA stem-loop structure forming at the ribosome binding site may control an initiation of translation . Stem-loop structures are also important in prokaryotic rho-independent transcription termination . The hairpin loop forms in an mRNA strand during transcription and causes

2343-518: 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. Telomerase is an RNP enzyme that adds specific DNA sequence repeats ("TTAGGG" in vertebrates) to telomeric regions, which are found at the ends of eukaryotic chromosomes . The telomeres contain condensed DNA material, giving stability to

2414-510: 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. Internal ribosome entry sites (IRES) are RNA structures that allow for translation initiation in

2485-531: The alternative splicing of mRNA, for example snoRNA HBII-52 regulates the splicing of serotonin receptor 2C . In nematodes, the SmY ncRNA appears to be involved in mRNA trans-splicing . 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

2556-399: The nucleus where it coats the inactive X chromosome. Alternatively spliced transcript variants have been identified, but their full length sequences have not been determined. The functional role of the Xist transcript was definitively demonstrated in mouse female ES cells using a novel antisense technology, called peptide nucleic acid (PNA) interference mapping. In the reported experiments,

2627-418: 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 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

2698-498: 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 ;

2769-453: 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

2840-599: The 48 copies of the C/D box snoRNA SNORD116 has been shown to be the primary cause of Prader–Willi syndrome . Prader–Willi is a developmental disorder associated with over-eating and learning difficulties. SNORD116 has potential target sites within a number of protein-coding genes, and could have a role in regulating alternative splicing. The chromosomal locus containing the small nucleolar RNA SNORD115 gene cluster has been duplicated in approximately 5% of individuals with autistic traits . A mouse model engineered to have

2911-418: 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. In eukaryotes,

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2982-514: 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

3053-410: The X and autosomal chromosomes. Different species have different dosage compensation methods, with all of the methods involving the regulation of an X chromosome from one of the either sexes. Some methods involved in dosage compensation to inactivate one of the X chromosomes from one of the sexes are Tsix antisense gene, DNA methylation and DNA acetylation; however, the definite mechanism of X-inactivation

3124-479: The X-inactivation centre (XIC), which plays a major role in Xist expression and X-inactivation. The XIC is located on the q arm of the X chromosome (Xq13). XIC regulates Xist in cis X-inactivation, where Tsix, an antisense of Xist, downregulates the expression of Xist. The Xist promoter of XIC is the master regulator of X-inactivation. X-inactivation plays a key role in dosage compensation. The Tsix antisense gene

3195-516: 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. Germline 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. It has been suggested that

3266-417: The absence of Tsix in pluripotent cells, Xist is repressed, where a mechanism has been proposed that these transcription factors cause splicing to occur at intron 1 at the binding site of these factors on the Xist gene, which inhibits Xist expression A study was conducted where Nanog or Oct4 transcription factors were depleted in pluripotent cells, which resulted in the upregulation of Xist. From this study, it

3337-537: The act of transcription of ncRNA sequence can have an influence on gene expression. RNA polymerase II transcription of ncRNAs is required for chromatin remodelling in the Schizosaccharomyces pombe . Chromatin is progressively converted to an open configuration, as several species of ncRNAs are transcribed. 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,

3408-466: The base composition of the paired region. Pairings between guanine and cytosine have three hydrogen bonds and are more stable compared to adenine - uracil pairings, which have only two. In RNA, adenine-uracil pairings featuring two hydrogen bonds are equal to the adenine- thymine bond of DNA. Base stacking interactions, which align the pi bonds of the bases' aromatic rings in a favorable orientation, also promote helix formation. The stability of

3479-408: The base-stacking interactions of its component nucleotides. Therefore, such loops can form on the microsecond time scale. Stem-loops occur in pre- microRNA structures and most famously in transfer RNA , which contain three true stem-loops and one stem that meet in a cloverleaf pattern. The anticodon that recognizes a codon during the translation process is located on one of the unpaired loops in

3550-447: The blastocyte forms. There, the imprint is removed, leading to the downregulation of Xist and thus reactivation of the inactive X chromosome. Recent data suggests that Xist activity is regulated by an anti-sense transcript. The epiblast cells are then formed and they begin to be differentiated, and the Xist is upregulated from either of the two X chromosomes and at random in ICM , but the Xist

3621-430: The chromosomes. The enzyme is a reverse transcriptase that carries Telomerase RNA , which is used as a template when it elongates telomeres, which are shortened after each replication cycle . Xist (X-inactive-specific transcript) is a long ncRNA gene on the X chromosome of the placental mammals that acts as major effector of the X chromosome inactivation process forming Barr bodies . An antisense RNA , Tsix ,

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3692-600: The discovery of the RNAi mechanism associated with the latter earned Craig C. 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 . 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

3763-706: The expression levels of hundreds of genes. The mechanism by which mature miRNA molecules act is through partial complementarity 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. It has been shown that 7SK RNA ,

3834-399: The expression of BACE1 by increasing BACE1 mRNA stability and generating additional BACE1 through a post-transcriptional feed-forward mechanism. By the same mechanism it also raises concentrations of beta amyloid , the main constituent of senile plaques. BACE1-AS concentrations are elevated in subjects with Alzheimer's disease and in amyloid precursor protein transgenic mice. Variation within

3905-477: 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 SR1 RNA , and Spot 42 RNA . ) Bifunctional RNAs were

3976-419: The loop also influences the formation of the stem-loop structure. Optimal loop length tends to be about 4-8 bases long; loops that are fewer than three bases long are sterically impossible and thus do not form, and large loops with no secondary structure of their own (such as pseudoknot pairing) are unstable. One common loop with the sequence UUCG is known as the " tetraloop ," and is particularly stable due to

4047-499: The middle of a mRNA sequence as part of the process of protein synthesis . 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 germline cells, particularly those in spermatogenesis . Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) are repeats found in

4118-467: 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 . 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

4189-566: The one missing or abnormal X chromosome. Turner's syndrome is also referred to as a monosomy X condition. Xist expression and X-inactivation change throughout embryonic development. In early embryogenesis, the oocyte and sperm do not express Xist and the X chromosome remains active. After fertilization, when the cells are in the 2 to 4 cell stage, Xist transcripts are expressed from paternal X chromosome(Xp) in every cell, causing that X chromosome to become imprinted and inactivated. Some cells develop into pluripotent cells (the inner cell mass) when

4260-504: The onset of XCI. SUZ12 is a component of the PRC2 and contains a zinc finger domain. The zinc finger domain is believed to bind to the RNA molecule. The PRC2 has been observed to repress Xist expression independent of the Tsix antisense transcript, although the definite mechanism is still not known. X-inactivation plays a key role in dosage compensation mechanisms that allow for equal expression of

4331-686: The ortholog does not feature conserved repeats. The Xist RNA gene is located within the Xist Inactivation Center (XIC), which plays a major role in X-inactivation. The Xist RNA contains a region of conservation called the repeat A (repA) region that contains up to nine repeated elements. It was initially suggested that repA repeats could fold back on themselves to form local intra-repeat stem-loop structures. Later work using in vitro biochemical structure probing proposed several inter-repeat stem-loop structures. A recent study using in vivo biochemical probing and comparative sequence analysis proposed

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4402-419: The pair of X chromosomes , thus providing dosage equivalence between males and females (see dosage compensation ). The process is regulated by several factors, including a region of chromosome X called the X-inactivation center (XIC). The XIST gene is expressed exclusively from the XIC of the inactive X chromosome. The transcript is spliced but apparently does not encode a protein . The transcript remains in

4473-427: The same nucleic acid strand, usually complementary in nucleotide sequence, base-pair to form a double helix that ends in a loop of unpaired nucleotides. Stem-loops are most commonly found in RNA, and are a key building block of many RNA secondary structures . Stem-loops can direct RNA folding, protect structural stability for messenger RNA (mRNA), provide recognition sites for RNA binding proteins , and serve as

4544-577: The seed region of mature miR-96 has been associated with autosomal dominant , progressive hearing loss in humans and mice. The homozygous mutant mice were profoundly deaf, showing no cochlear responses. Heterozygous mice and humans progressively lose the ability to hear. A number of mutations within mitochondrial tRNAs have been linked to diseases such as MELAS syndrome , MERRF syndrome , and chronic progressive external ophthalmoplegia . Scientists have started to distinguish functional RNA ( fRNA ) from ncRNA, to describe regions functional at

4615-463: The subject of a 2011 special issue of Biochimie . There is an important link between certain non-coding RNAs and the control of hormone-regulated pathways. In Drosophila , hormones such as ecdysone and juvenile hormone can promote the expression of certain miRNAs. Furthermore, this regulation occurs at distinct temporal points within Caenorhabditis elegans development. In mammals, miR-206

4686-461: The tRNA. Two nested stem-loop structures occur in RNA pseudoknots , where the loop of one structure forms part of the second stem. Many ribozymes also feature stem-loop structures. The self-cleaving hammerhead ribozyme contains three stem-loops that meet in a central unpaired region where the cleavage site lies. The hammerhead ribozyme's basic secondary structure is required for self-cleavage activity. Hairpin loops are often elements found within

4757-492: The transcription of Xist. A dsRNA and RNAi pathway have been also proposed to play a role in regulation of the Xist Promoter. Dicer is an RNAi enzyme and it is believed to cleave the duplex of Xist and Tsix at the beginning of X-inactivation, to small ~30 nucleotide RNAs, which have been termed xiRNAs, These xiRNAs are believed to be involved in repressing Xist on the probable active X chromosome based upon studies. A study

4828-402: Was conducted where normal endogenous Dicer levels were decreased to 5%, which led to an increase in Xist expression in undifferentiated cells, thus supporting the role of xiRNAs in Xist repression. The role and mechanism of xiRNAs is still under examination and debate. Pluripotent stem cells express transcription factors Nanog , Oct4 and Sox2 that seem to play a role in repressing Xist. In

4899-450: Was functionally mapped and evaluated by using an approach for studying noncoding RNA function in living cells called peptide nucleic acid (PNA) interference mapping. In the reported experiments, a single 19-bp antisense cell-permeating PNA targeted against a particular region of Xist RNA caused the disruption of the Xi. The association of the Xi with macro-histone H2A is also disturbed by PNA interference mapping. The Xist RNA gene lies within

4970-455: 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 ). 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,

5041-506: Was shown that the entire region is needed for efficient binding to the Suz12 protein. The Xist RNA directly binds to the inactive X-chromosome through a chromatin binding region of the RNA transcript. The Xist chromatin binding region was first elucidated in female mouse fibroblastic cells. The primary chromatin binding region was shown to localize to the C-repeat region. The chromatin-binding region

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