Cytoplasmic localization of pseudouridine synthase 7 facilitates a pseudouridine-dependent enhancement of cellular stress tolerance
Pseudouridine (Ψ) is an abundant post-transcriptional modification found across all classes of RNA. It is widely speculated that Ψ inclusion in messenger RNAs (mRNAs) might provide an avenue for cells to control gene expression post-transcriptionally. Here we demonstrate that one of the principal mRNA pseudouridylating enzymes, pseudouridine synthase 7 (PUS7), exhibits a stress-induced accumulation in the cytoplasm of yeast and human epithelial lung cells. Stress-induced and cytoplasmic localization of PUS7 promotes Ψ-incorporation into hundreds of mRNA targets. In contrast, the modification status of tRNA sites targeted by PUS7 (Ψ13 and Ψ35) is unperturbed. Furthermore, engineered PUS7 cytoplasmic localization increases cellular fitness under reactive oxygen species (ROS) and divalent metal ion stress. Quantitative proteomics reveal a reshaping of the proteome upon PUS7 relocalization under stress. Collectively, our data demonstrate that PUS7 localization alters mRNA pseudouridylation patterns, reshapes the proteome, and influences cellular fitness.
Authors
- Stuart Akeson (ORCID: https://orcid.org/0009-0008-8008-2486)
- Kristin S. Koutmou (ORCID: https://orcid.org/0000-0002-7763-9262)
- Chase A. Weidmann (ORCID: https://orcid.org/0000-0002-2941-0500)
- Miten Jain (ORCID: https://orcid.org/0000-0002-4571-3982)
- Matthew R. Burroughs (ORCID: https://orcid.org/0009-0007-1611-647X)
- Dylan Bloch (ORCID: https://orcid.org/0000-0002-5382-5765)
- Sara H. Rouhanifard (ORCID: https://orcid.org/0000-0002-6991-4877)
- Sean M. Engels (ORCID: https://orcid.org/0000-0002-4866-6050)
- Lydia M. Contreras (ORCID: https://orcid.org/0000-0001-5010-5511)
- Minli Ruan
- Oleksandra Fanari (ORCID: https://orcid.org/0009-0003-2915-859X)
- Daniel E. Eyler (ORCID: https://orcid.org/0000-0002-6425-9770)
- Rosella Stower
- Connor Powell (ORCID: https://orcid.org/0009-0006-6889-0099)
- Xiaoyan Li
- Talia Tzadikario
Institutions
- Northeastern University (US)
- University of Michigan (US)
- The University of Texas at Austin (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-04-17
- DOI
- https://doi.org/10.1038/s41467-026-71654-y
- Citations
- 1
- Primary Topic
- RNA modifications and cancer
- Type
- article
- Field-Weighted Citation Impact
- 12.01
Funders
- National Science Foundation
- Foundation for the National Institutes of Health
- American Heart Association
- National Institutes of Health