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In molecular biology, competing endogenous RNAs (abbreviated ''ceRNAs'') regulate other RNA transcripts by competing for shared microRNAs. == Summary == MicroRNAs (miRNA) are an abundant class of small, non-coding RNAs (~22nt long), which negatively regulate gene expression at the levels of messenger RNAs (mRNAs) stability and translation inhibition. The human genome consists of over 500 miRNA, each one targeting hundreds of different genes. It is estimated that half of all genes of the genome are targets of miRNA, spanning a large layer of regulation on a post-transcriptional level. The seed region, which comprises nucleotides 2-8 of the 5’ portion of the miRNA, is particularly crucial for mRNA recognition and silencing. Recent studies have shown that the interaction of the miRNA seed region with mRNA is not unidirectional, but that the pool of mRNAs, transcribed pseudogenes, long noncoding RNAs (lncRNA), circular RNA (circRNA) compete for the same pool of miRNA.〔 These competitive endogenous RNAs (ceRNAs) act as molecular sponges for a microRNA through their miRNA binding sites (also referred to as miRNA response elements, MRE), thereby de-repressing all target genes of the respective miRNA family. Experimental evidence for such a ceRNA crosstalk has been initially shown for the tumor suppressor gene PTEN, which is regulated by the 3’ untranslated region (3'UTR) of the pseudogene PTENP1 in a DICER-dependent manner. RNA transcripts, both protein-coding and non-coding, thus have the ability to compete for microRNA binding and co-regulate each other in complex ceRNA networks (ceRNETs). The ceRNA language represents an added trans-regulatory dimension to RNA biology and suggests that even protein-coding genes can function as RNA, independently of their protein-coding function. The prediction and identification of ceRNAs for a given RNA enables the functionalization of the transcriptome irrespective of whether transcripts encode for proteins. The characterization of a breast-cancer ceRNET has been used to improve miRNA-target prediction. The biological relevance of the ceRNA hypothesis is being actively debated. It has recently been challenged by the quantitative assessment of miR-122 and its binding sites in liver. The authors reported that very high numbers of competing target sites had to be added to observe ceRNA mediated effects, suggesting that ceRNA are unlikely to regulate the availability of miR-122 in liver cells. Bosson et al. addressed these findings, suggesting that ceRNA is unlikely to alter the activity of highly abundant miRNAs such as miR-122 in liver cells. Supported by biochemical measurements in single cells, they found that ceRNA regulation is less likely to affect miRNAs with very high or very low abundance, but can substantially alter the activity of medium-abundance miRNAs. A more recent report found changes in miR-122 binding in liver cells due to ceRNA regulation. 抄文引用元・出典: フリー百科事典『 ウィキペディア(Wikipedia)』 ■ウィキペディアで「Competing endogenous RNA (CeRNA)」の詳細全文を読む スポンサード リンク
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