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A Large-Scale Binding and Functional Map of Human RNA Binding Proteins

Eric L Van Nostrand, Peter Freese, Gabriel A Pratt, Xiaofeng Wang, Xintao Wei, Rui Xiao, Steven M Blue, Jia-Yu Chen, Neal A.L. Cody, Daniel Dominguez, Sara Olson, Balaji Sundararaman, Lijun Zhan, Cassandra Bazile, Louis Philip Benoit Bouvrette, Julie Bergalet, Michael O Duff, Keri E. Garcia, Chelsea Gelboin-Burkhart, Myles Hochman, Nicole J Lambert, Hairi Li, Thai B Nguyen, Tsultrim Palden, Ines Rabano, Shashank Sathe, Rebecca Stanton, Amanda Su, Ruth Wang, Brian A. Yee, Bing Zhou, Ashley L Louie, Stefan Aigner, Xiang-dong Fu, Eric Lécuyer, Christopher B. Burge, Brenton R. Graveley, Gene W. Yeo
doi: https://doi.org/10.1101/179648
Eric L Van Nostrand
1Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA
2Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA
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Peter Freese
3Program in Computational and Systems Biology, MIT Cambridge MA
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Gabriel A Pratt
1Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA
2Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA
4Bioinformatics and Systems Biology Graduate Program, University of California San Diego, La Jolla, CA
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Xiaofeng Wang
5Institut de Recherches Cliniques de Montréal (IRCM), Montreal, Canada
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Xintao Wei
6Department of Genetics and Genome Sciences, Institute for Systems Genomics, UConn Health, Farmington, CT
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Rui Xiao
1Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA
2Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA
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Steven M Blue
1Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA
2Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA
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Jia-Yu Chen
1Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA
2Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA
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Neal A.L. Cody
5Institut de Recherches Cliniques de Montréal (IRCM), Montreal, Canada
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Daniel Dominguez
7Department of Biology, MIT, Cambridge MA
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Sara Olson
6Department of Genetics and Genome Sciences, Institute for Systems Genomics, UConn Health, Farmington, CT
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Balaji Sundararaman
1Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA
2Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA
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Lijun Zhan
6Department of Genetics and Genome Sciences, Institute for Systems Genomics, UConn Health, Farmington, CT
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Cassandra Bazile
7Department of Biology, MIT, Cambridge MA
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Louis Philip Benoit Bouvrette
5Institut de Recherches Cliniques de Montréal (IRCM), Montreal, Canada
9Department of Biochemistry and Molecular Medicine, Université de Montréal, Montreal, Canada
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Julie Bergalet
5Institut de Recherches Cliniques de Montréal (IRCM), Montreal, Canada
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Michael O Duff
6Department of Genetics and Genome Sciences, Institute for Systems Genomics, UConn Health, Farmington, CT
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Keri E. Garcia
1Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA
2Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA
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Chelsea Gelboin-Burkhart
1Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA
2Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA
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Myles Hochman
7Department of Biology, MIT, Cambridge MA
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Nicole J Lambert
7Department of Biology, MIT, Cambridge MA
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Hairi Li
1Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA
2Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA
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Thai B Nguyen
1Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA
2Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA
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Tsultrim Palden
7Department of Biology, MIT, Cambridge MA
8Department of Biological Engineering, MIT, Cambridge MA
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Ines Rabano
1Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA
2Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA
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Shashank Sathe
1Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA
2Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA
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Rebecca Stanton
1Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA
2Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA
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Amanda Su
7Department of Biology, MIT, Cambridge MA
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Ruth Wang
1Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA
2Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA
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Brian A. Yee
1Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA
2Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA
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Bing Zhou
1Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA
2Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA
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Ashley L Louie
1Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA
2Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA
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Stefan Aigner
1Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA
2Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA
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Xiang-dong Fu
1Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA
2Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA
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  • For correspondence: graveley@uchc.edu cburge@mit.edu xdfu@ucsd.edu eric.lecuyer@ircm.qc.ca geneyeo@ucsd.edu
Eric Lécuyer
5Institut de Recherches Cliniques de Montréal (IRCM), Montreal, Canada
9Department of Biochemistry and Molecular Medicine, Université de Montréal, Montreal, Canada
10Division of Experimental Medicine, McGill University, Montreal, Canada
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  • For correspondence: graveley@uchc.edu cburge@mit.edu xdfu@ucsd.edu eric.lecuyer@ircm.qc.ca geneyeo@ucsd.edu
Christopher B. Burge
3Program in Computational and Systems Biology, MIT Cambridge MA
7Department of Biology, MIT, Cambridge MA
8Department of Biological Engineering, MIT, Cambridge MA
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  • For correspondence: graveley@uchc.edu cburge@mit.edu xdfu@ucsd.edu eric.lecuyer@ircm.qc.ca geneyeo@ucsd.edu
Brenton R. Graveley
6Department of Genetics and Genome Sciences, Institute for Systems Genomics, UConn Health, Farmington, CT
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  • For correspondence: graveley@uchc.edu cburge@mit.edu xdfu@ucsd.edu eric.lecuyer@ircm.qc.ca geneyeo@ucsd.edu
Gene W. Yeo
1Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA
2Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA
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  • For correspondence: graveley@uchc.edu cburge@mit.edu xdfu@ucsd.edu eric.lecuyer@ircm.qc.ca geneyeo@ucsd.edu
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Abstract

Genomes encompass all the information necessary to specify the development and function of an organism. In addition to genes, genomes also contain a myriad of functional elements that control various steps in gene expression. A major class of these elements function only when transcribed into RNA as they serve as the binding sites for RNA binding proteins (RBPs), which act to control post-transcriptional processes including splicing, cleavage and polyadenylation, RNA editing, RNA localization, stability, and translation. Despite the importance of these functional RNA elements encoded in the genome, they have been much less studied than genes and DNA elements. Here, we describe the mapping and characterization of RNA elements recognized by a large collection of human RBPs in K562 and HepG2 cells. These data expand the catalog of functional elements encoded in the human genome by addition of a large set of elements that function at the RNA level through interaction with RBPs.

  • 223 eCLIP datasets for 150 RBPs reveal a wide variety of in vivo RNA target classes.

  • 472 knockdown/RNA-seq profiles of 263 RBPs reveal factor-responsive targets and integration with eCLIP indicates RNA expression and splicing regulatory patterns.

  • 78 RNA Bind-N-Seq profiles of in vitro binding motifs reveal links between in vitro and in vivo binding and indicate that eCLIP peaks that contain in vitro motifs are more strongly associated with regulation.

  • 274 maps of RBP subcellular localization by immunofluorescence indicate widespread organelle-specific RNA processing regulation.

  • 63 ChIP-seq profiles of DNA association suggest broad interconnectivity between chromatin association and RNA processing.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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A Large-Scale Binding and Functional Map of Human RNA Binding Proteins
Eric L Van Nostrand, Peter Freese, Gabriel A Pratt, Xiaofeng Wang, Xintao Wei, Rui Xiao, Steven M Blue, Jia-Yu Chen, Neal A.L. Cody, Daniel Dominguez, Sara Olson, Balaji Sundararaman, Lijun Zhan, Cassandra Bazile, Louis Philip Benoit Bouvrette, Julie Bergalet, Michael O Duff, Keri E. Garcia, Chelsea Gelboin-Burkhart, Myles Hochman, Nicole J Lambert, Hairi Li, Thai B Nguyen, Tsultrim Palden, Ines Rabano, Shashank Sathe, Rebecca Stanton, Amanda Su, Ruth Wang, Brian A. Yee, Bing Zhou, Ashley L Louie, Stefan Aigner, Xiang-dong Fu, Eric Lécuyer, Christopher B. Burge, Brenton R. Graveley, Gene W. Yeo
bioRxiv 179648; doi: https://doi.org/10.1101/179648
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A Large-Scale Binding and Functional Map of Human RNA Binding Proteins
Eric L Van Nostrand, Peter Freese, Gabriel A Pratt, Xiaofeng Wang, Xintao Wei, Rui Xiao, Steven M Blue, Jia-Yu Chen, Neal A.L. Cody, Daniel Dominguez, Sara Olson, Balaji Sundararaman, Lijun Zhan, Cassandra Bazile, Louis Philip Benoit Bouvrette, Julie Bergalet, Michael O Duff, Keri E. Garcia, Chelsea Gelboin-Burkhart, Myles Hochman, Nicole J Lambert, Hairi Li, Thai B Nguyen, Tsultrim Palden, Ines Rabano, Shashank Sathe, Rebecca Stanton, Amanda Su, Ruth Wang, Brian A. Yee, Bing Zhou, Ashley L Louie, Stefan Aigner, Xiang-dong Fu, Eric Lécuyer, Christopher B. Burge, Brenton R. Graveley, Gene W. Yeo
bioRxiv 179648; doi: https://doi.org/10.1101/179648

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