PUS7 cytoplasmic localization directs a pseudouridine-mediated cellular stress response (CU-OOH)

ABSTRACT: Pseudouridine is an abundant post-transcriptional modification found across all classes of RNA. Since its discovery in mRNAs a decade ago, it has been widely speculated that Y might govern additional post-transcriptional regulation of gene expression. Here, we demonstrate that one of the principal enzymes responsible for adding Y to mRNAs, pseudouridine synthase 7 (PUS7), accumulates in the cytoplasm under a variety of stress conditions in Saccharomyces cerevisiae and BEAS-2B human epithelial lung cells. The localization of PUS7 to the cytoplasm promotes Y-incorporation into hundreds of different mRNA sequences and increases cellular fitness under ROS and divalent metal ion stress. The preponderance of newly identified Y-sites lies within portions of the mRNA important for post-transcriptional control—-coding regions and 3’ UTRs. Quantitative proteomics reveal that shifts in the cellular post-transcriptional modification landscape upon PUS7 relocalization reshapes the proteome. Our data suggest a mechanism whereby stressors localize PUS7 in the cytoplasm to enable the direct modification and regulation of stress response mRNAs, thereby protecting cells from further stress-induced damage. (PUS7-NES_CU_1A 75059 PUS7-NES_CU_1B 75060 PUS7-NES_CU_1C 75061 PUS7-NLS_CU_2A 75062 PUS7-NLS_CU_2B 75063 PUS7-NLS_CU_2C 75064 PUS7-WT_CU_3A 75065 PUS7-WT_CU_3B 75066 PUS7-WT_CU_3C 75067))

INSTRUMENT(S):

ORGANISM(S): Saccharomyces Cerevisiae (baker's Yeast)

SUBMITTER: Minli Ruan  

LAB HEAD: Kristin Koutmou

PROVIDER: PXD073675 | Pride | 2026-01-28

REPOSITORIES: Pride