Translation suppresses exogenous target RNA-mediated microRNA decay

MicroRNAs (miRNAs) are a class of non-coding RNAs that interact with the target mRNAs to induce translational repression and mRNA degradation. Generally, miRNAs are stable when associating with the effector protein Argonaute (AGO). However, miRNA can turnover rapidly when binding to a target RNA with extensive complementarity, a phenomenon called target-directed miRNA degradation (TDMD). To date, most validated "TDMD trigger" sequences that can induce miRNA degradation reside in non-coding regions of the RNA. We found that when an engineered TDMD trigger was placed in the 3 untranslated region (UTR) of a green fluorescent protein (GFP) reporter, it induced more significant miRNA degradation than when the trigger was placed in the coding sequence (CDS). Inhibiting translation of the GFP reporter enhanced miRNA degradation by the CDS trigger, but not the 3 UTR trigger. This is because CDS triggers become more accessible to miRNAs free from the translating ribosomes. By small RNA sequencing, we identified miRNAs sensitive to global translation status. Yet, few CDS triggers could be confidently assigned to these miRNAs. Our work explains the paucity of effective TDMD triggers in the CDS and suggests potential dysregulation of miRNA levels due to impaired translation.