SIDER2 retroposon-mediated mRNA decay in Leishmania is coupled to translation

•We report the first known demonstration of a co-translational mRNA decay mechanism in trypanosomatids.•Inhibition of translation blocks decay of SIDER2 retroposon-containing transcripts.•Rapid turnover of Leishmania transcripts mediated by SIDER2 retroposons is coupled to ongoing translation.•These findings provide new mechanistic insights into one of the major regulated mRNA decay pathways in Leishmania.

We previously reported that Short Interspersed Degenerate Retroposons of the SIDER2 subfamily predominantly located within 3′ untranslated regions (UTRs) of Leishmania transcripts promote rapid turnover that is initiated by endonucleolytic cleavage. Here, we investigated whether SIDER2-mediated mRNA decay is linked to translation. We show that preventing translation initiation by inserting a hairpin structure at the 5′-end of a SIDER2-containing mRNA blocks degradation. Similarly, global inhibition of translation elongation by cycloheximide or termination by puromycin causes stabilisation of SIDER2-containing transcripts. Altogether, these findings support that the mechanism of SIDER2-mediated decay is coupled to translation, possibly through the recruitment of decay factors to elongating ribosomes.

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