U1 snRNP regulates chromatin retention of noncoding RNAs

doi:10.1038/s41586-020-2105-3

GSTDTAP > 地球科学

DOI	10.1038/s41586-020-2105-3
	U1 snRNP regulates chromatin retention of noncoding RNAs
	Dehollain, J. P.1,2,7; Mukhopadhyay, U.1,2; Michal, V. P.1,2; Wang, Y.3; Wunsch, B.3; Reichl, C.4; Wegscheider, W.4; Rudner, M. S.5,6; Demler, E.3; Vandersypen, L. M. K.1,2
	2020-03-02
发表期刊	NATURE
ISSN	0028-0836
EISSN	1476-4687
出版年	2020
文章类型	Article;Early Access
语种	英语
国家	Peoples R China; USA
英文关键词	Long noncoding RNAs (lncRNAs) and promoter- or enhancer-associated unstable transcripts locate preferentially to chromatin, where some regulate chromatin structure, transcription and RNA processing(1-13). Although several RNA sequences responsible for nuclear localization have been identified-such as repeats in the lncRNA Xist and Alu-like elements in long RNAs14-16-how lncRNAs as a class are enriched at chromatin remains unknown. Here we describe a random, mutagenesis-coupled, high-throughput method that we name ' RNA elements for subcellular localization by sequencing' (mutREL-seq). Using this method, we discovered an RNA motif that recognizes the U1 small nuclear ribonucleoprotein (snRNP) and is essential for the localization of reporter RNAs to chromatin. Across the genome, chromatin-bound lncRNAs are enriched with 5 ' splice sites and depleted of 3 ' splice sites, and exhibit high levels of U1 snRNA binding compared with cytoplasm-localized messenger RNAs. Acute depletion of U1 snRNA or of the U1 snRNP protein component SNRNP70 markedly reduces the chromatin association of hundreds of lncRNAs and unstable transcripts, without altering the overall transcription rate in cells. In addition, rapid degradation of SNRNP70 reduces the localization of both nascent and polyadenylated lncRNA transcripts to chromatin, and disrupts the nuclear and genome-wide localization of the lncRNA Malat1. Moreover, U1 snRNP interacts with transcriptionally engaged RNA polymerase II. These results show that U1 snRNP acts widely to tether and mobilize lncRNAs to chromatin in a transcription-dependent manner. Our findings have uncovered a previously unknown role of U1 snRNP beyond the processing of precursor mRNA, and provide molecular insight into how lncRNAs are recruited to regulatory sites to carry out chromatin-associated functions. Long noncoding RNAs and certain unstable transcripts tend to localize to chromatin, in a process that is shown here to depend on an RNA motif that recognizes the small nuclear ribonuclear protein U1, and to rely on transcription.
领域	地球科学 ; 气候变化 ; 资源环境
收录类别	SCI-E
WOS记录号	WOS:000519162500005
WOS关键词	PRE-MESSENGER-RNAS ; GENE-EXPRESSION ; HUMAN GENOME ; XIST RNA ; TRANSCRIPTION ; POLYADENYLATION ; REVEALS ; DIFFERENTIATION ; LOCALIZATION ; INITIATION
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/281333
专题	地球科学资源环境科学气候变化
作者单位	1.Delft Univ Technol, QuTech, Delft, Netherlands; 2.Delft Univ Technol, Kavli Inst Nanosci, Delft, Netherlands; 3.Harvard Univ, Dept Phys, Cambridge, MA 02138 USA; 4.Swiss Fed Inst Technol, Solid State Phys Lab, Zurich, Switzerland; 5.Univ Copenhagen, Niels Bohr Inst, Ctr Quantum Devices, Copenhagen, Denmark; 6.Univ Copenhagen, Niels Bohr Int Acad, Niels Bohr Inst, Copenhagen, Denmark; 7.Univ Technol Sydney, Sch Math & Phys Sci, Sydney, NSW, Australia
推荐引用方式 GB/T 7714	Dehollain, J. P.,Mukhopadhyay, U.,Michal, V. P.,et al. U1 snRNP regulates chromatin retention of noncoding RNAs[J]. NATURE,2020.
APA	Dehollain, J. P..,Mukhopadhyay, U..,Michal, V. P..,Wang, Y..,Wunsch, B..,...&Vandersypen, L. M. K..(2020).U1 snRNP regulates chromatin retention of noncoding RNAs.NATURE.
MLA	Dehollain, J. P.,et al."U1 snRNP regulates chromatin retention of noncoding RNAs".NATURE (2020).