Mechanism of translational regulation by miR-2 from sites in the 5′ untranslated region or the open reading frame
Mechanism of translational regulation by miR-2 from sites in the 5′ untranslated region or the open reading frame
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DOI：
10.1261/rna.2384610
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发表时间：
2010-12-01
期刊：
影响因子：
4.5
通讯作者：
Hentze, Matthias W.
中科院分区：
文献类型：
--
作者：
Moretti, Francesca;Thermann, Rolf;Hentze, Matthias W.
MicroRNAs(MiRs)通常调节来自靶mRNA3‘非翻译区(UTRs)的翻译。虽然在5‘非翻译区(UTRs)或开放阅读框(ORF)中也发现了有效的miR结合位点，但这些位点介导miR调控的机制(S)尚未确定。在这里，我们系统地研究miR结合位点的位置如何影响翻译调控，并表征它们的机制基础。我们发现，在体外和体内，不仅从3‘UTR中诱导出特异性的翻译调节，而且从5’UTR或ORF中的6个果蝇miR2结合位点也同样有效。在所有情况下，miR-2都以帽依赖的方式触发mRNA去烯化并抑制翻译启动。相反，5‘UTR或ORF中的单个或双miR-2结合位点产生相当低的效率或没有调节。这项工作首次证明了5‘UTR和ORF miR结合位点可以发挥与深入研究的3’UTR位点类似的机械功能。使用单或双结合位点，它也揭示了3‘UTR中miR调节位点高发的生物学基础。
MicroRNAs (miRs) commonly regulate translation from target mRNA 3' untranslated regions (UTRs). While effective miR-binding sites have also been identified in 5' untranslated regions (UTRs) or open reading frames (ORFs), the mechanism(s) of miR-mediated regulation from these sites has not been defined. Here, we systematically investigate how the position of miR-binding sites influences translational regulation and characterize their mechanistic basis. We show that specific translational regulation is elicited in vitro and in vivo not only from the 3'UTR, but equally effectively from six Drosophila miR2-binding sites in the 5'UTR or the ORF. In all cases, miR-2 triggers mRNA deadenylation and inhibits translation initiation in a cap-dependent fashion. In contrast, single or dual miR-2-binding sites in the 5'UTR or the ORF yield rather inefficient or no regulation. This work represents the first demonstration that 5'UTR and ORF miR-binding sites can function mechanistically similarly to the intensively investigated 3'UTR sites. Using single or dual binding sites, it also reveals a biological rationale for the high prevalence of miR regulatory sites in the 3'UTR.