Faculty, Staff and Student Publications

Language

English

Publication Date

6-6-2025

Journal

Nature Communications

DOI

10.1038/s41467-025-60374-4

PMID

40480978

PMCID

PMC12144122

PubMedCentral® Posted Date

6-6-2025

PubMedCentral® Full Text Version

Post-print

Abstract

MicroRNAs (miRNAs) interact with the target mRNAs to induce translational repression and mRNA degradation. Interestingly, miRNAs themselves can turnover rapidly when binding to a target RNA with extensive complementarity, a phenomenon called target-directed miRNA degradation (TDMD). To date, all validated TDMD "triggers" can induce miRNA degradation reside in non-coding regions of the RNA. We found that TDMD triggers placed in the 3' untranslated region (UTR) of a reporter degraded miRNAs more effectively than those in the coding sequence (CDS). Inhibiting translation of the reporter enhanced miRNA degradation by the CDS trigger, indicating that ribosome-free CDS triggers are more accessible to miRNAs. By small RNA sequencing, we explored mammalian miRNAs sensitive to global translation status. Yet, no endogenous CDS trigger could be confidently assigned to these miRNAs. Our work revealed the intricate relationship between translation and TDMD, and explains the paucity of effective TDMD triggers in the CDS.

Keywords

MicroRNAs, Protein Biosynthesis, Humans, RNA Stability, 3' Untranslated Regions, RNA, Messenger, Animals, HEK293 Cells, Mice, miRNAs, Gene regulation, RNA

Published Open-Access

yes

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