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PMID: 32728246 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

A large-scale binding and functional map of human RNA-binding proteins.

Nature ·Vol. 583 ·No. 7818 ·2020-00-00 ·Pages 711-719

Van Nostrand EL, Freese P, Pratt GA, Wang X, Wei X, Xiao R, Blue SM, Chen JY, Cody NAL, Dominguez D, Olson S, Sundararaman B, Zhan L, Bazile C, Bouvrette LPB, Bergalet J, Duff MO, Garcia KE, Gelboin-Burkhart C, Hochman M, Lambert NJ, Li H, McGurk MP, Nguyen TB, Palden T, Rabano I, Sathe S, Stanton R, Su A, Wang R, Yee BA, Zhou B, Louie AL, Aigner S, Fu XD, Lécuyer E, Burge CB, Graveley BR, Yeo GW

Abstract

Many proteins regulate the expression of genes by binding to specific regions encoded in the genome1. Here we introduce a new data set of RNA elements in the human genome that are recognized by RNA-binding proteins (RBPs), generated as part of the Encyclopedia of DNA Elements (ENCODE) project phase III. This class of regulatory elements functions only when transcribed into RNA, as they serve as the binding sites for RBPs that control post-transcriptional processes such as splicing, cleavage and polyadenylation, and the editing, localization, stability and translation of mRNAs. We describe the mapping and characterization of RNA elements recognized by a large collection of human RBPs in K562 and HepG2 cells. Integrative analyses using five assays identify RBP binding sites on RNA and chromatin in vivo, the in vitro binding preferences of RBPs, the function of RBP binding sites and the subcellular localization of RBPs, producing 1,223 replicated data sets for 356 RBPs. We describe the spectrum of RBP binding throughout the transcriptome and the connections between these interactions and various aspects of RNA biology, including RNA stability, splicing regulation and RNA localization. These data expand the catalogue of functional elements encoded in the human genome by the addition of a large set of elements that function at the RNA level by interacting with RBPs.

MeSH Terms
Alternative Splicing/genetics Base Sequence Binding Sites Cell Line Chromatin/genetics,metabolism Databases, Genetic Female Gene Knockdown Techniques Humans Intracellular Space/genetics Male Protein Binding RNA, Messenger/chemistry,genetics,metabolism RNA-Binding Proteins/chemistry,genetics,metabolism Substrate Specificity Transcriptome/genetics
Chemicals
Chromatin RNA, Messenger RNA-Binding Proteins
Authors & Affiliations
39 authors, click to expand affiliations / ORCID
Van Nostrand Eric L ORCID
Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA. | Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA.
Freese Peter
Program in Computational and Systems Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
Pratt Gabriel A
Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA. | Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA. | Bioinformatics and Systems Biology Graduate Program, University of California San Diego, La Jolla, CA, USA.
Wang Xiaofeng
Institut de Recherches Cliniques de Montréal (IRCM), Montreal, Quebec, Canada.
Wei Xintao
Department of Genetics and Genome Sciences, Institute for Systems Genomics, UConn Health, Farmington, CT, USA.
Xiao Rui
Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA. | Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA. | Medical Research Institute, Wuhan University, Wuhan, China.
Blue Steven M
Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA. | Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA.
Chen Jia-Yu ORCID
Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA. | Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA.
Cody Neal A L
Institut de Recherches Cliniques de Montréal (IRCM), Montreal, Quebec, Canada.
Dominguez Daniel
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
Olson Sara
Department of Genetics and Genome Sciences, Institute for Systems Genomics, UConn Health, Farmington, CT, USA.
Sundararaman Balaji ORCID
Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA. | Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA.
Zhan Lijun
Department of Genetics and Genome Sciences, Institute for Systems Genomics, UConn Health, Farmington, CT, USA.
Bazile Cassandra
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
Bouvrette Louis Philip Benoit
Institut de Recherches Cliniques de Montréal (IRCM), Montreal, Quebec, Canada. | Department of Biochemistry and Molecular Medicine, Université de Montréal, Montreal, Quebec, Canada.
Bergalet Julie
Institut de Recherches Cliniques de Montréal (IRCM), Montreal, Quebec, Canada.
Duff Michael O
Department of Genetics and Genome Sciences, Institute for Systems Genomics, UConn Health, Farmington, CT, USA.
Garcia Keri E
Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA. | Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA.
Gelboin-Burkhart Chelsea
Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA. | Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA.
Hochman Myles
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
Lambert Nicole J
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
Li Hairi
Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA. | Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA.
McGurk Michael P
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
Nguyen Thai B
Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA. | Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA.
Palden Tsultrim
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA. | Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Rabano Ines ORCID
Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA. | Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA.
Sathe Shashank
Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA. | Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA.
Stanton Rebecca
Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA. | Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA.
Su Amanda
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
Wang Ruth
Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA. | Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA.
Yee Brian A
Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA. | Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA.
Zhou Bing ORCID
Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA. | Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA.
Louie Ashley L
Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA. | Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA.
Aigner Stefan ORCID
Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA. | Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA.
Fu Xiang-Dong ORCID
Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA. [email protected]. | Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA. [email protected].
Lécuyer Eric
Institut de Recherches Cliniques de Montréal (IRCM), Montreal, Quebec, Canada. [email protected]. | Department of Biochemistry and Molecular Medicine, Université de Montréal, Montreal, Quebec, Canada. [email protected]. | Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada. [email protected].
Burge Christopher B ORCID
Program in Computational and Systems Biology, Massachusetts Institute of Technology, Cambridge, MA, USA. [email protected]. | Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA. [email protected]. | Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. [email protected].
Graveley Brenton R
Department of Genetics and Genome Sciences, Institute for Systems Genomics, UConn Health, Farmington, CT, USA. [email protected].
Yeo Gene W
Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA. [email protected]. | Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA. [email protected]. | Bioinformatics and Systems Biology Graduate Program, University of California San Diego, La Jolla, CA, USA. [email protected].
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Article Info
Journal
Nature
Abbr.
Nature
ISSN
1476-4687
DOI
10.1038/s41586-020-2077-3
Email
[email protected]
[email protected]
[email protected]
[email protected]
[email protected]
Published
2020-00-00
Epub
2020-00-29
Pages
711-719
Language
English
Region
England
NLM ID
0410462
PMCID
PMC7410833
Subset
IM
Grants
NHGRI NIH HHS · R00 HG009530 · United States
NHGRI NIH HHS · U54 HG007005 · United States
NHGRI NIH HHS · U41 HG009889 · United States
NIGMS NIH HHS · T32 GM087237 · United States
NHGRI NIH HHS · R01 HG004659 · United States
NCI NIH HHS · R01 CA226898 · United States
NHGRI NIH HHS · K99 HG009530 · United States
Corrections
ErratumIn
PMID: 33402748
External Links
PubMed source DOI: 10.1038/s41586-020-2077-3 PMC Full Text View journal details
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