Translation suppresses exogenous target RNA-mediated microRNA decay

Tianqi Li, Lu Li, Nicholas M. Hiers, Peike Sheng, Yuzhi Wang, Conner M. Traugot, Jessi F. Effinger-Morris, Pitchaporn Akaphan, Yanyan Liu, Jiang Bian, Kotaro Fujii and Mingyi Xie ()
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Tianqi Li: University of Florida
Lu Li: University of Florida
Nicholas M. Hiers: University of Florida
Peike Sheng: University of Florida
Yuzhi Wang: University of Florida
Conner M. Traugot: University of Florida
Jessi F. Effinger-Morris: University of Florida
Pitchaporn Akaphan: University of Florida
Yanyan Liu: University of Florida
Jiang Bian: University of Florida
Kotaro Fujii: University of Florida
Mingyi Xie: University of Florida

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-60374-4

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