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Non-coding RNA
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===In gene regulation=== The [[Gene expression|expression]] of many thousands of [[gene]]s are regulated by ncRNAs. This regulation can occur in [[Trans-acting|trans]] or in [[Cis-acting|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.{{citation needed|date=June 2017}} ====Trans-acting==== In higher eukaryotes [[microRNA]]s 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 complementarity to one or more messenger RNA (mRNA) molecules, generally in [[Three prime untranslated region|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 ribosomal RNA|5S rRNA]], [[Signal recognition particle|SRP]] RNA, and [[U6 spliceosomal RNA|U6 snRNA]] genes. RNase P exerts its role in transcription through association with Pol III and [[chromatin]] of active tRNA and 5S rRNA genes.<ref name="pmid16778078">{{cite journal | vauthors = Reiner R, Ben-Asouli Y, Krilovetzky I, Jarrous N | title = A role for the catalytic ribonucleoprotein RNase P in RNA polymerase III transcription | journal = Genes & Development | volume = 20 | issue = 12 | pages = 1621β1635 | date = June 2006 | pmid = 16778078 | pmc = 1482482 | doi = 10.1101/gad.386706 }}</ref> It has been shown that [[7SK RNA]], a [[metazoan]] ncRNA, acts as a negative regulator of the [[RNA polymerase II]] [[elongation factor|elongation factor P-TEFb]], and that this activity is influenced by stress response pathways.{{citation needed|date=June 2017}} The bacterial ncRNA, [[6S RNA]], specifically associates with RNA polymerase holoenzyme containing the [[Sigma factor|sigma70]] specificity factor. This interaction represses expression from a sigma70-dependent [[promoter (biology)|promoter]] during [[Bacterial growth|stationary phase]].{{citation needed|date=June 2017}} Another bacterial ncRNA, [[OxyS RNA]] represses translation by binding to [[Shine-Dalgarno sequence]]s thereby occluding ribosome binding. OxyS RNA is induced in response to oxidative stress in Escherichia coli.{{citation needed|date=June 2017}} 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.<ref name="pmid15300239">{{cite journal | vauthors = Espinoza CA, Allen TA, Hieb AR, Kugel JF, Goodrich JA | title = B2 RNA binds directly to RNA polymerase II to repress transcript synthesis | journal = Nature Structural & Molecular Biology | volume = 11 | issue = 9 | pages = 822β829 | date = September 2004 | pmid = 15300239 | doi = 10.1038/nsmb812 | s2cid = 22199826 }}</ref> A recent study has shown that just 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.<ref name="pmid18820678">{{cite journal | vauthors = Hirota K, Miyoshi T, Kugou K, Hoffman CS, Shibata T, Ohta K | title = Stepwise chromatin remodelling by a cascade of transcription initiation of non-coding RNAs | journal = Nature | volume = 456 | issue = 7218 | pages = 130β134 | date = November 2008 | pmid = 18820678 | doi = 10.1038/nature07348 | s2cid = 4416402 | bibcode = 2008Natur.456..130H }}</ref> ====Cis-acting==== {{Main|Five prime untranslated region|Three prime untranslated region}} A number of ncRNAs are embedded in the 5' [[Untranslated Region|UTRs]] (Untranslated Regions) of [[mRNA|protein coding genes]] and influence their expression in various ways. For example, a [[riboswitch]] can directly bind a [[Small molecule|small target molecule]]; the binding of the target affects the gene's activity.{{citation needed|date=June 2017}} [[Attenuator (genetics)|RNA leader]] sequences are found upstream of the first gene of amino acid biosynthetic operons. These [[cis-regulatory element|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. 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]].{{citation needed|date=June 2017}} [[Iron response element]]s (IRE) are bound by [[Iron-responsive element binding protein|iron response proteins]] (IRP). The IRE is found in UTRs of various [[mRNA]]s whose products are involved in [[iron metabolism]]. When iron concentration is low, IRPs bind the ferritin mRNA IRE leading to translation repression.{{citation needed|date=June 2017}} [[Internal ribosome entry site]]s (IRES) are [[RNA structure]]s that allow for [[translation (genetics)|translation]] initiation in the middle of a mRNA sequence as part of the process of [[protein synthesis]].{{citation needed|date=June 2017}}
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