U1 snRNP regulates chromatin retention of noncoding RNAs

被引:146
作者
Yin, Yafei [1 ,2 ]
Lu, J. Yuyang [1 ,2 ]
Zhang, Xuechun [1 ,2 ]
Shao, Wen [1 ,2 ]
Xu, Yanhui [1 ,2 ]
Li, Pan [1 ,2 ,3 ]
Hong, Yantao [1 ,2 ]
Cui, Li [1 ,2 ]
Shan, Ge [4 ]
Tian, Bin [5 ,6 ]
Zhang, Qiangfeng Cliff [1 ,2 ,3 ]
Shen, Xiaohua [1 ,2 ]
机构
[1] Tsinghua Univ, Sch Med, Tsinghua Peking Joint Ctr Life Sci, Beijing, Peoples R China
[2] Tsinghua Univ, Sch Life Sci, Beijing, Peoples R China
[3] Tsinghua Univ, Beijing Adv Innovat Ctr Struct Biol, Beijing, Peoples R China
[4] Univ Sci & Technol China, Sch Life Sci, Hefei, Anhui, Peoples R China
[5] Rutgers New Jersey Med Sch, Dept Microbiol Biochem & Mol Genet, Newark, NJ USA
[6] Rutgers Canc Inst New Jersey, Newark, NJ USA
基金
中国国家自然科学基金; 美国国家卫生研究院;
关键词
PRE-MESSENGER-RNAS; GENE-EXPRESSION; HUMAN GENOME; XIST RNA; TRANSCRIPTION; POLYADENYLATION; REVEALS; DIFFERENTIATION; LOCALIZATION; INITIATION;
D O I
10.1038/s41586-020-2105-3
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:147 / +
页数:25
相关论文
共 50 条
[31]   RNA-RNA Interactions Enable Specific Targeting of Noncoding RNAs to Nascent Pre-mRNAs and Chromatin Sites [J].
Engreitz, Jesse M. ;
Sirokman, Klara ;
McDonel, Patrick ;
Shishkin, Alexander A. ;
Surka, Christine ;
Russell, Pamela ;
Grossman, Sharon R. ;
Chow, Amy Y. ;
Guttman, Mitchell ;
Lander, Eric S. .
CELL, 2014, 159 (01) :188-199
[32]   Nuclear Fractionation Reveals Thousands of Chromatin-Tethered Noncoding RNAs Adjacent to Active Genes [J].
Werner, Michael S. ;
Ruthenburg, Alexander J. .
CELL REPORTS, 2015, 12 (07) :1089-1098
[33]   The U1 snRNP Subunit LUC7 Modulates Plant Development and Stress Responses via Regulation of Alternative Splicing [J].
Amorim, Marcella de Francisco ;
Willing, Eva-Maria ;
Szabo, Emese X. ;
Francisco-Mangilet, Anchilie G. ;
Droste-Borel, Irina ;
Macek, Boris ;
Schneeberger, Korbinian ;
Laubinger, Sascha .
PLANT CELL, 2018, 30 (11) :2838-2854
[34]   Long Noncoding RNAs: At the Intersection of Cancer and Chromatin Biology [J].
Schmitt, Adam M. ;
Chang, Howard Y. .
COLD SPRING HARBOR PERSPECTIVES IN MEDICINE, 2017, 7 (07) :1-16
[35]   U1 snRNP increases RNA Pol II elongation rate to enable synthesis of long genes [J].
Mimoso, Claudia A. ;
Adelman, Karen .
MOLECULAR CELL, 2023, 83 (08) :1264-+
[36]   FUS functions in coupling transcription to splicing by mediating an interaction between RNAP II and U1 snRNP [J].
Yu, Yong ;
Reed, Robin .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2015, 112 (28) :8608-8613
[37]   Regulation of chromatin structure by long noncoding RNAs: focus on natural antisense transcripts [J].
Magistri, Marco ;
Faghihi, Mohammad Ali ;
St Laurent, Georges, III ;
Wahlestedt, Claes .
TRENDS IN GENETICS, 2012, 28 (08) :389-396
[38]   Genome-wide RNA-binding analysis of the trypanosome U1 snRNP proteins U1C and U1-70K reveals cis/trans-spliceosomal network [J].
Preusser, Christian ;
Rossbach, Oliver ;
Hung, Lee-Hsueh ;
Li, Dan ;
Bindereif, Albrecht .
NUCLEIC ACIDS RESEARCH, 2014, 42 (10) :6603-6615
[39]   Transcriptional Pause Sites Delineate Stable Nucleosome-Associated Premature Polyadenylation Suppressed by U1 snRNP [J].
Chiu, Anthony C. ;
Suzuki, Hiroshi I. ;
Wu, Xuebing ;
Mahat, Dig B. ;
Kriz, Andrea J. ;
Sharp, Phillip A. .
MOLECULAR CELL, 2018, 69 (04) :648-+
[40]   Comprehensive RNP profiling in cells identifies U1 snRNP complexes with cleavage and polyadenylation factors active in telescripting [J].
Cai, Zhiqiang ;
So, Byung Ran ;
Dreyfuss, Gideon .
MRNA 3' END PROCESSING AND METABOLISM, 2021, 655 :325-347