Translation suppresses exogenous target RNA-mediated microRNA decay

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. Stable microRNAs (miRNAs) can undergo turnover via target-directed miRNA degradation (TDMD). Here, the authors show that TDMD triggers in non-coding regions degrade miRNAs more effectively than those in coding regions, where translation interferes with this process.