Newly synthesized mRNA escapes translational repression during the acute phase of the mammalian unfolded protein response

• DOI: 10.1371/journal.pone.0271695
• Publication Date: 2022-08-10T17:33:13Z
• Authors: Mohammed R. Alzah...; Bo-Jhih Guan; Leah L. Zagore; Jing Wu; Chien-Wen Chen; Donny D. Licatalosi; Kristian E. Baker; Maria Hatzoglou
• Keywords: XBP1; Translational regulation; Translational efficiency; Transcription

Endoplasmic Reticulum (ER) stress, caused by the accumulation of misfolded proteins in ER, elicits a homeostatic mechanism known as Unfolded Protein Response (UPR). The UPR reprograms gene expression to promote adaptation chronic ER stress. comprises an acute phase involving inhibition bulk protein synthesis and transcriptional induction coupled with partial recovery synthesis. However, role regulation is not well understood. Here we analyzed fate newly synthesized mRNA encoding protective transcription factor X-box binding 1 (XBP1) during this phase. We have previously shown that global translational repression induced was characterized decreased translation increased stability XBP1 mRNA. demonstrate here stabilization independent new transcription. In contrast, show accumulates long poly(A) tails escapes repression. Inhibition RNA polyadenylation cell survival no effect unstressed cells. Furthermore, UPR, levels manner consistent co-translational deadenylation. Finally, additional pro-survival, transcriptionally-induced mRNAs similar regulation, supporting broad significance pre-steady state control conclude biphasic tail length represents unrecognized pro-survival mammalian regulation.