1. A novel class of microRNA-recognition elements that function only within open reading frames
- Author
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Zhang, Kai, Zhang, Xiaorong, Cai, Zhiqiang, Zhou, Jie, Cao, Ran, Zhao, Ya, Chen, Zonggui, Wang, Dehe, Ruan, Wen, Zhao, Qian, Liu, Guangqiao, Xue, Yuanchao, Qin, Yan, Zhou, Bing, Wu, Ligang, Nilsen, Timothy, Zhou, Yu, and Fu, Xiang-Dong
- Subjects
Biotechnology ,Genetics ,1.1 Normal biological development and functioning ,Underpinning research ,Generic health relevance ,3' Untranslated Regions ,Argonaute Proteins ,Autoantigens ,Base Pairing ,Gene Expression Regulation ,Gene Silencing ,HeLa Cells ,Humans ,MicroRNAs ,Models ,Biological ,Open Reading Frames ,Protein Biosynthesis ,RNA Recognition Motif ,RNA Stability ,RNA ,Messenger ,RNA-Binding Proteins ,Ribosomes ,Hela Cells ,Chemical Sciences ,Biological Sciences ,Medical and Health Sciences ,Biophysics ,Developmental Biology - 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.
- Published
- 2018