Translation suppresses exogenous target RNA-mediated microRNA decay
Open Access
- 6 June 2025
- journal article
- research article
- Published by Springer Nature in Nature Communications
- Vol. 16 (1) , 1-17
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
Funding Information
- U.S. Department of Health & Human Services | National Institutes of Health (R35GM128753, R01CA282812, T32AI007110)
- American Cancer Society (RSG-21-118-01-RMC)
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