Transcriptome-wide Mapping Reveals Widespread Dynamic-Regulated Pseudouridylation of ncRNA and mRNA

被引：778

作者：

Schwartz, Schraga ^{[1
]}

Bernstein, Douglas A. ^{[2
]}

Mumbach, Maxwell R. ^{[1
]}

Jovanovic, Marko ^{[1
]}

Herbst, Rebecca H. ^{[1
,3
]}

Leon-Ricardo, Brian X. ^{[1
,4
]}

Engreitz, Jesse M. ^{[1
,5
]}

Guttman, Mitchell ^{[6
]}

Satija, Rahul ^{[1
]}

Lander, Eric S. ^{[1
,3
,7
]}

Fink, Gerald ^{[2
,7
]}

Regev, Aviv ^{[1
,7
,8
]}

机构：

[1] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[2] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA

[3] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02114 USA

[4] Univ Puerto Rico, Dept Biol, San Juan, PR 00931 USA

[5] MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA

[6] CALTECH, Div Biol & Biol Engn, Pasadena, CA 91125 USA

[7] MIT, Dept Biol, Cambridge, MA 02139 USA

[8] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA

来源：

CELL | 2014年 / 159卷 / 01期

基金：

瑞士国家科学基金会;

关键词：

ACID SECONDARY STRUCTURE; RIBOSOMAL-RNA; SACCHAROMYCES-CEREVISIAE; DYSKERATOSIS-CONGENITA; TELOMERASE RNA; PEPTIDYLTRANSFERASE CENTER; CHEMICAL-MODIFICATION; CARBODIIMIDE REAGENT; U2; SNRNA; YEAST;

D O I：

10.1016/j.cell.2014.08.028

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 Psi-seq for transcriptome-wide quantitative mapping of pseudouridine. We validate Psi-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.

引用

页码：148 / 162

页数：15

共 56 条

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