Transcriptome-wide Mapping Reveals Widespread Dynamic-Regulated Pseudouridylation of ncRNA and mRNA
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Lander_Transcriptome-wide.pdf
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Author(s)
Schwartz, Schraga
Bernstein, Douglas A.
Mumbach, Maxwell R.
Jovanovic, Marko
Herbst, Rebecca H.
León-Ricardo, Brian X.
Guttman, Mitchell
Satija, Rahul
Fink, Gerald
Engreitz, Jesse Michael
Date Issued
September 2014
Journal
Cell
Publisher
Elsevier
Citation
Schwartz, Schraga et al. “Transcriptome-Wide Mapping Reveals Widespread Dynamic-Regulated Pseudouridylation of ncRNA and mRNA.” Cell 159.1 (2014): 148–162.
Version
Author's final manuscript
Abstract
Pseudouridine is the most abundant RNA modification, yet except for a few well-studied cases, little is known about the modified positions and their function(s). Here, we develop Ψ-seq for transcriptome-wide quantitative mapping of pseudouridine. We validate Ψ-seq with spike-ins and de novo identification of previously reported positions and discover hundreds of unique sites in human and yeast mRNAs and snoRNAs. Perturbing pseudouridine synthases (PUS) uncovers which pseudouridine synthase modifies each site and their target sequence features. mRNA pseudouridinylation depends on both site-specific and snoRNA-guided pseudouridine synthases. Upon heat shock in yeast, Pus7p-mediated pseudouridylation is induced at >200 sites, and PUS7 deletion decreases the levels of otherwise pseudouridylated mRNA, suggesting a role in enhancing transcript stability. rRNA pseudouridine stoichiometries are conserved but reduced in cells from dyskeratosis congenita patients, where the PUS DKC1 is mutated. Our work identifies an enhanced, transcriptome-wide scope for pseudouridine and methods to dissect its underlying mechanisms and function.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.cell.2014.08.028
