期刊
CELL
卷 161, 期 2, 页码 404-416出版社
CELL PRESS
DOI: 10.1016/j.cell.2015.03.025
关键词
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资金
- NIH [NS069375, P50-HG007735]
- California Institute for Regenerative Medicine
- Equipe labellisee La Ligue Contre Le Cancer (Equipe Labellise)
- Labex DEEP, IDEX Idex PSL [ANR-11-LBX-0044, ANR-10-IDEX-000102 PSL]
- EpiGeneSys Network of Excellence [FP7 257082]
- ERC [250367]
- European Research Council (ERC) [250367] Funding Source: European Research Council (ERC)
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.
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