Translation elongation inhibitors stabilize select transcripts

The ribosome is central to cellular stress responses because it serves as a sensor to activate signaling pathways that determine cell fate. While the activation of these signaling pathways by translation elongation inhibitors has been well characterized, the impact of these inhibitors on mRNA dynamics remains unclear. 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 compositions of these stabilized transcripts are suboptimal compared to short-lived mRNAs that are not stabilized. Finally, we show that stabilization of these transcripts is independent of the signaling pathways activated by ribosome collisions, as well as of canonical ribosome quality control factors. Our data describe a group of transcripts whose degradation is particularly sensitive to the inhibition of translation elongation. Overall design: HEK-293T cells were treated with 500 µM 4-thiouridine (s4U) and with 1.8 µM emetine for 1 hour or left untreated. For 2 hour treatments, cells were incubated with 250µM s4U and treated with 1.8µM or 240µM emetine.TimeLapse sequencing was then performed and samples were sequenced on a Nova-seq platform.