MicroRNA (miRNA) are well known to target 3 untranslated regions (3UTR) in mRNAs to silence gene expression at post-transcriptional levels. Multiple reports have also indicated the capability of miRNAs to target protein-coding sequences (CDS); however, miRNAs have been generally believed to function in a similar mechanism(s) regardless of the location of their action sites. We herein report a class of miRNA recognition elements (MREs) that exclusively function in CDS regions in humans. Through functional and mechanistic characterization of these unusual MREs, we demonstrate that CDS-targeted miRNAs require extensive base pairings in 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 for miRNAs to target CDS versus 3UTR and suggest that CDS-targeted miRNAs may enlist a translational quality control (QC)-related mechanism to regulate translation in mammalian cells. SOURCE: Xiang-Dong FuGeorge Palade Laboratories UC San Diego

Pluto Bioinformatics

GSE115146: A Novel Class of MicroRNA Recognition Elements That Function Only in Open Reading Frames