Transcriptome-wide mapping reveals widespread dynamic regulated pseudouridylation of ncRNA and mRNA

By Schraga Schwartz, D. Bernstein, Maxwell R Mumbach, M. Jovanović, Rebecca H. Herbst, Brian X. León-Ricardo, J. Engreitz, M. Guttman, Rahul Satija, Eric S. Lander and 2 more. Cell, 2014

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SUMMARY 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 novel sites in human and yeast mRNAs and snoRNAs. Perturbing pseudouridine synthases (PUSs) uncovers which PUSs modify each site and their target sequence features. mRNA pseudouridinylation depends on both site-specific and snoRNA-guided PUSs. Upon heat shock in yeast, Pus7-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, transcritome-wide scope for pseudouridine, and methods to dissect its underlying mechanisms and function.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/7d0e1c7226f6e0dad8c37811cb6feaf4d1a57129

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Citations in the corpus

Tuning the ribosome: The influence of rRNA modification on eukaryotic ribosome biogenesis and function (2016, background): “For example, after diauxic shift a 2-fold change in the extent of 25S-C2314 was detected122 and heat-shock was observed to alter the fraction of 5S-C50 that is modified by Pus7.”
Accurate detection of m6A RNA modifications in native RNA sequences (2019, methodology): “Consequently, indirect methods are required to identify RNA modifications transcriptome-wide, which has been mainly approached using two different strategies: (i) antibody immunoprecipitation, which specifically recognizes the modified ribonucleotide [5,6,12–14]; and (ii) chemical-based detection, u”
Rethinking m6A Readers, Writers, and Erasers (2017, methodology): “Shortly after these seminal discoveries, the WTAP-METTL3 interaction was confirmed in diverse mammalian cells (Liu et al. 2014, Ping et al. 2014, Schwartz et al. 2014b).”
RNA N6-methyladenosine methylation in post-transcriptional gene expression regulation (2015, background): “In addition tom6A, recent studies have characterized the distribution of pseudouridine as another widespread and dynamic modification of mRNA (Carlile et al. 2014; Schwartz et al. 2014a).”
N6-methyladenosine Modulates Messenger RNA Translation Efficiency (2015, neutral): “, 2012), pseudouridine (Carlile et al., 2014; Schwartz et al., 2014), and N-methyladenosinde (Fu et al.”