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A novel class of microRNA-recognition elements that function only within open reading frames, Nat Struct Mol Biol, 8 Oct 2018

发布时间:2018年10月08日

Nature Structural & Molecular Biology, 8 October 2018,DOI: http://dx.doi.org/10.1038/s41594-018-0136-3

A novel class of microRNA-recognition elements that function only within open reading frames

Kai Zhang, Xiaorong Zhang, Zhiqiang Cai, Jie Zhou, Ran Cao, Ya Zhao, Zonggui Chen, Dehe Wang, Wen Ruan, Qian Zhao, Guangqiao Liu, Yuanchao Xue, Yan Qin, Bing Zhou, Ligang Wu, Timothy Nilsen, Yu Zhou & Xiang-Dong Fu

Abstract

MicroRNAs (miRNAs) are well known to target 3′ untranslated regions (3′ UTRs) in mRNAs, thereby silencing gene expression at the post-transcriptional level. Multiple reports have also indicated the ability of miRNAs to target protein-coding sequences (CDS); however, miRNAs have been generally believed to function through similar mechanisms regardless of the locations of their sites of action. Here, we report a class of miRNA-recognition elements (MREs) that function exclusively in CDS regions. Through functional and mechanistic characterization of these ‘unusual’ MREs, we demonstrate that CDS-targeted miRNAs require extensive base-pairing at the 3′ side rather than the 5′ seed; cause gene silencing in an Argonaute-dependent but GW182-independent manner; and repress translation by inducing transient ribosome stalling instead of mRNA destabilization. These findings reveal distinct mechanisms and functional consequences of miRNAs that target CDS versus the 3′ UTR and suggest that CDS-targeted miRNAs may use a translational quality-control-related mechanism to regulate translation in mammalian cells.

文章链接:https://www.nature.com/articles/s41594-018-0136-3

 

 

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