Poster abstracts
Poster number 121 submitted by Minli Ruan
PUS7 cytoplasmic localization directs a pseudouridine-mediated cellular stress response
Minli Ruan (University of Michigan, Department of Biological Chemistry, Ann Arbor, MI 48109), Sean M. Engels, Matthew R. Burroughs, Lydia M. Contreras (University of Texas, McKetta Department of Chemical Engineering, Austin, TX 78712), Dylan Bloch, Oleksandra Fanari, Stuart Akeson, Sara Rouhanifard, Miten Jain (Northeastern University, Department of Bioengineering, Boston, MA 02120), Daniel E. Eyler, Xiaoyan Li (University of Michigan, Department of Chemistry, Ann Arbor, MI 48109), Chase A. Weidmann (University of Michigan, Department of Biological Chemistry, Ann Arbor, MI 48109), Kristin S. Koutmou (University of Michigan, Department of Chemistry, Ann Arbor, MI 48109)
Abstract:
Pseudouridine (Y) is an abundant post-transcriptional modification found across all classes of RNA. Since its discovery in mRNAs, it has been widely speculated that Y might provide an avenue for cells to control post-transcriptional gene expression. 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. The cytoplasmic localization of PUS7 promotes Y-incorporation into hundreds of mRNA sequences and increases cellular fitness under ROS and divalent metal ion stress. Quantitative proteomics reveal a reshaping of the proteome upon PUS7 relocalization under stress, with proteins that bind metal being particularly sensitive. Collectively, our data demonstrate that the post-transcriptional inclusion of Y into mRNA impacts protein production in cells. Furthermore, they suggest a conserved mechanism for a Y-mediated cellular stress response, whereby stressors relocalize PUS7 and modulate protein production from stress response mRNAs.
References:
1. Eyler, D. E. et al. Pseudouridinylation of mRNA coding sequences alters translation. Proc Natl Acad Sci USA 116, 23068–23074 (2019).
2. Carlile, T. M. et al. Pseudouridine profiling reveals regulated mRNA pseudouridylation in yeast and human cells. Nature 515, 143–146 (2014).
3. Schwartz, S. et al. Transcriptome-wide mapping reveals widespread dynamic-regulated pseudouridylation of ncRNA and mRNA. Cell 159, 148–162 (2014).
Keywords: Pseudouridine, PUS7, Gene regulation