Translation elongation inhibitors stabilize select short-lived transcripts

Abstract

Translation elongation inhibitors are commonly used to study different cellular processes. Yet, their specific impact on transcription and mRNA decay has not been thoroughly assessed. Here we use TimeLapse sequencing to investigate how translational stress impacts mRNA dynamics in human cells. Our results reveal that a distinct group of transcripts is stabilized in response to the translation elongation inhibitor emetine. These stabilized mRNAs are short-lived at steady state and many of them encode C2H2 zinc finger proteins. The codon usage of these stabilized transcripts is suboptimal compared to other expressed transcripts, including other short-lived mRNAs that are not stabilized after emetine treatment. Finally, we show that stabilization of these transcripts is independent of ribosome quality control factors and signaling pathways activated by ribosome collisions. Our data describe a group of short-lived transcripts whose degradation is particularly sensitive to the inhibition of translation elongation.