PUS7 cytoplasmic localization directs a pseudouridine-mediated cellular stress response (CU-OOH)
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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.
INSTRUMENT(S):
ORGANISM(S): Saccharomyces Cerevisiae (baker's Yeast)
SUBMITTER:
Minli Ruan
LAB HEAD: Minli Ruan
PROVIDER: PXD073675 | Pride | 2026-01-28
REPOSITORIES: Pride
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