Systematic Discovery of Xist RNA Binding Proteins

被引：914

作者：

Chu, Ci ^{[1
,2
,3
]}

Zhang, Qiangfeng Cliff ^{[1
,2
]}

da Rocha, Simao Teixeira ^{[4
]}

Flynn, Ryan A. ^{[1
,2
]}

Bharadwaj, Maheetha ^{[1
,2
]}

Calabrese, J. Mauro ^{[5
,6
]}

Magnuson, Terry ^{[6
,7
]}

Heard, Edith ^{[4
]}

Chang, Howard Y. ^{[1
,2
]}

机构：

[1] Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA

[2] Stanford Univ, Sch Med, Program Epithelial Biol, Stanford, CA 94305 USA

[3] Genome Inst Singapore, Singapore 138672, Singapore

[4] Inst Curie, CNRS UMR3215, INSERM U934, F-75248 Paris, France

[5] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA

[6] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA

[7] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA

来源：

CELL | 2015年 / 161卷 / 02期

基金：

欧洲研究理事会;

关键词：

X-CHROMOSOME INACTIVATION; EMBRYONIC STEM-CELLS; LONG NONCODING RNAS; U1; SNRNP; CRYSTAL-STRUCTURE; PRC2; RECRUITMENT; HISTONE H2A; POLYCOMB; MOUSE; PLURIPOTENCY;

D O I：

10.1016/j.cell.2015.03.025

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Noncoding RNAs (ncRNAs) function with associated proteins to effect complex structural and regulatory outcomes. To reveal the composition and dynamics of specific noncoding RNA-protein complexes (RNPs) in vivo, we developed comprehensive identification of RNA binding proteins by mass spectrometry (ChIRP-MS). ChIRP-MS analysis of four ncRNAs captures key protein interactors, including a U1-specific link to the 3' RNA processing machinery. Xist, an essential lncRNA for X chromosome inactivation (XCI), interacts with 81 proteins from chromatin modification, nuclear matrix, and RNA remodeling pathways. The Xist RNA-protein particle assembles in two steps coupled with the transition from pluripotency to differentiation. Specific interactors include HnrnpK, which participates in Xist-mediated gene silencing and histone modifications but not Xist localization, and Drosophila Split ends homolog Spen, which interacts via the A-repeat domain of Xist and is required for gene silencing. Thus, Xist lncRNA engages with proteins in a modular and developmentally controlled manner to coordinate chromatin spreading and silencing.

引用

页码：404 / 416

页数：13

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