The role of RNA structure at 5' untranslated region in microRNA-mediated gene regulation.

The role of RNA structure at 5' untranslated region in microRNA-mediated gene regulation.
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DOI:
10.1261/rna.044792.114
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发表时间:
2014-09
期刊:
RNA (New York, N.Y.)
影响因子:
--
通讯作者:
Zhou T
Zhou T
中科院分区:
其他
文献类型:
--
作者:
Gu W;Xu Y;Xie X;Wang T;Ko JH;Zhou T

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一项系统的调查显示,在动物中受miRNA调节的mrna中,靠近5 ‘帽的5 ’ UTR中的二级结构水平增加,而在植物中则没有。最近的研究表明,信使RNA (mRNA)的5 ‘非翻译区(5 ’ UTR)的二级结构对人类microRNA (miRNA)介导的基因调控很重要。被miRNA靶向的mrna往往在其5 ' UTR中具有较高程度的局部二级结构;然而,5 ' UTR在mirna介导的基因调控中的一般作用尚不清楚。我们系统地调查了植物和动物物种中5 ‘ utr的二级结构,发现在受miRNA调节的mRNA中,在5 ’帽附近的mRNA稳定性普遍增加,而在植物中则不增加。基因组内比较表明,基因表达水平、5 ' UTR的GC含量、miRNA靶位点数量和5 ‘ UTR长度可能影响5 ’帽附近的mRNA结构。我们的研究结果表明,5 ' UTR二级结构在调节转录后过程中具有多种功能。虽然起始密码子上游的局部结构参与翻译起始,但在mirna介导的基因调控中起重要作用的是靠近5 ' cap位点的RNA结构,而不是全长5 ' UTR序列的结构。
A systematic survey shows increased levels of secondary structure in the 5′ UTR near the 5′ cap in mRNAs that are regulated by miRNA in animals, but not in plants. Recent studies have suggested that the secondary structure of the 5′ untranslated region (5′ UTR) of messenger RNA (mRNA) is important for microRNA (miRNA)-mediated gene regulation in humans. mRNAs that are targeted by miRNA tend to have a higher degree of local secondary structure in their 5′ UTR; however, the general role of the 5′ UTR in miRNA-mediated gene regulation remains unknown. We systematically surveyed the secondary structure of 5′ UTRs in both plant and animal species and found a universal trend of increased mRNA stability near the 5′ cap in mRNAs that are regulated by miRNA in animals, but not in plants. Intra-genome comparison showed that gene expression level, GC content of the 5′ UTR, number of miRNA target sites, and 5′ UTR length may influence mRNA structure near the 5′ cap. Our results suggest that the 5′ UTR secondary structure performs multiple functions in regulating post-transcriptional processes. Although the local structure immediately upstream of the start codon is involved in translation initiation, RNA structure near the 5′ cap site, rather than the structure of the full-length 5′ UTR sequences, plays an important role in miRNA-mediated gene regulation.
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