Analysis of CDS-located miRNA target sites suggests that they can effectively inhibit translation.

Analysis of CDS-located miRNA target sites suggests that they can effectively inhibit translation.
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DOI:
10.1101/gr.139758.112
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发表时间:
2013-04
期刊:
影响因子:
7
通讯作者:
Zavolan M
Zavolan M
中科院分区:
生物学1区
文献类型:
--
作者:
Hausser J;Syed AP;Bilen B;Zavolan M

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目前关于miRNA如何调节基因表达的大部分知识来自于对位于mRNA 3′非翻译区(UTR)的miRNA结合位点的调节作用的研究。近年来,越来越多的证据表明,miRNA也结合在编码区(CDS),但这些相互作用的含义仍然不清楚,因为它们对mRNA稳定性的影响比涉及3′ UTR的miRNA-靶相互作用小。在这里,我们表明,位于CDS和3′-UTR的miRNA互补位点都处于选择压力下,并且具有相同的序列和结构特性。从miRNA互补位点的角度分析最近发表的miRNA转染后核糖体保护片段谱的数据,我们发现位于CDS的位点在抑制翻译方面最有效,而位于3′ UTR的位点在触发mRNA降解方面更有效。我们的研究表明,miRNAs可能通过联合收割机靶向CDS和3′ UTR,灵活地调节其转录后调控作用的时间尺度和大小。
Most of what is presently known about how miRNAs regulate gene expression comes from studies that characterized the regulatory effect of miRNA binding sites located in the 3′ untranslated regions (UTR) of mRNAs. In recent years, there has been increasing evidence that miRNAs also bind in the coding region (CDS), but the implication of these interactions remains obscure because they have a smaller impact on mRNA stability compared with miRNA-target interactions that involve 3′ UTRs. Here we show that miRNA-complementary sites that are located in both CDS and 3′-UTRs are under selection pressure and share the same sequence and structure properties. Analyzing recently published data of ribosome-protected fragment profiles upon miRNA transfection from the perspective of the location of miRNA-complementary sites, we find that sites located in the CDS are most potent in inhibiting translation, while sites located in the 3′ UTR are more efficient at triggering mRNA degradation. Our study suggests that miRNAs may combine targeting of CDS and 3′ UTR to flexibly tune the time scale and magnitude of their post-transcriptional regulatory effects.
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