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PMID: 27720645 Published · ppublish English Journal Article

SONAR Discovers RNA-Binding Proteins from Analysis of Large-Scale Protein-Protein Interactomes.

Molecular cell ·Vol. 64 ·No. 2 ·2016-00-20 ·Pages 282-293

Brannan KW, Jin W, Huelga SC, Banks CA, Gilmore JM, Florens L, Washburn MP, Van Nostrand EL, Pratt GA, Schwinn MK, Daniels DL, Yeo GW

Abstract

RNA metabolism is controlled by an expanding, yet incomplete, catalog of RNA-binding proteins (RBPs), many of which lack characterized RNA binding domains. Approaches to expand the RBP repertoire to discover non-canonical RBPs are currently needed. Here, HaloTag fusion pull down of 12 nuclear and cytoplasmic RBPs followed by quantitative mass spectrometry (MS) demonstrates that proteins interacting with multiple RBPs in an RNA-dependent manner are enriched for RBPs. This motivated SONAR, a computational approach that predicts RNA binding activity by analyzing large-scale affinity precipitation-MS protein-protein interactomes. Without relying on sequence or structure information, SONAR identifies 1,923 human, 489 fly, and 745 yeast RBPs, including over 100 human candidate RBPs that contain zinc finger domains. Enhanced CLIP confirms RNA binding activity and identifies transcriptome-wide RNA binding sites for SONAR-predicted RBPs, revealing unexpected RNA binding activity for disease-relevant proteins and DNA binding proteins.

Keywords
RNA-binding proteins machine-learning protein-protein interaction networks support vector machine
MeSH Terms
Algorithms Animals Binding Sites Cell Nucleus/chemistry,metabolism Cytoplasm/chemistry,metabolism Drosophila melanogaster/genetics,metabolism Gene Expression Gene Ontology HEK293 Cells Humans Molecular Sequence Annotation Nucleotide Motifs Protein Binding Protein Interaction Domains and Motifs RNA/chemistry,genetics,metabolism RNA-Binding Proteins/chemistry,classification,genetics,metabolism Saccharomyces cerevisiae/genetics,metabolism Software Zinc Fingers
Chemicals
RNA-Binding Proteins RNA
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Brannan Kristopher W
Department of Cellular and Molecular Medicine, Stem Cell Program and Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Jin Wenhao
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 117597 Singapore, Singapore.
Huelga Stephanie C
Department of Cellular and Molecular Medicine, Stem Cell Program and Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Banks Charles A S
Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
Gilmore Joshua M
Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
Florens Laurence
Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
Washburn Michael P
Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA; Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
Van Nostrand Eric L
Department of Cellular and Molecular Medicine, Stem Cell Program and Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Pratt Gabriel A
Department of Cellular and Molecular Medicine, Stem Cell Program and Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Schwinn Marie K
Promega Corporation, 2800 Woods Hollow Road, Madison, WI 53711, USA.
Daniels Danette L
Promega Corporation, 2800 Woods Hollow Road, Madison, WI 53711, USA.
Yeo Gene W
Department of Cellular and Molecular Medicine, Stem Cell Program and Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 117597 Singapore, Singapore; Molecular Engineering Laboratory, A(∗)STAR, 138673 Singapore, Singapore. Electronic address: [email protected].
References (34)
34 references, click to expand
  1. A human interactome in three quantitative dimensions organized by stoichiometries and abundances.
    Cell. 2015 Oct 22;163(3):712-23 PMID: 26496610
  2. A census of human RNA-binding proteins.
    Nat Rev Genet. 2014 Dec;15(12 ):829-45 PMID: 25365966
  3. Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.
    Cell. 2012 Jun 8;149(6):1393-406 PMID: 22658674
  4. RNA-binding proteins in human genetic disease.
    Trends Genet. 2008 Aug;24(8):416-25 PMID: 18597886
  5. Proteome-wide search reveals unexpected RNA-binding proteins in Saccharomyces cerevisiae.
    PLoS One. 2010 Sep 10;5(9):null PMID: 20844764
  6. Widespread RNA binding by chromatin-associated proteins.
    Genome Biol. 2016 Feb 16;17 :28 PMID: 26883116
  7. Serial interactome capture of the human cell nucleus.
    Nat Commun. 2016 Apr 04;7:11212 PMID: 27040163
  8. Quantitative proteomic analysis reveals concurrent RNA-protein interactions and identifies new RNA-binding proteins in Saccharomyces cerevisiae.
    Genome Res. 2013 Jun;23(6):1028-38 PMID: 23636942
  9. Refinements to label free proteome quantitation: how to deal with peptides shared by multiple proteins.
    Anal Chem. 2010 Mar 15;82(6):2272-81 PMID: 20166708
  10. Robust transcriptome-wide discovery of RNA-binding protein binding sites with enhanced CLIP (eCLIP).
    Nat Methods. 2016 Jun;13(6):508-14 PMID: 27018577
  11. BioGRID: a general repository for interaction datasets.
    Nucleic Acids Res. 2006 Jan 1;34(Database issue):D535-9 PMID: 16381927
  12. TET2 and TET3 regulate GlcNAcylation and H3K4 methylation through OGT and SET1/COMPASS.
    EMBO J. 2013 Mar 6;32(5):645-55 PMID: 23353889
  13. Characterization of phosphorylation- and RNA-dependent UPF1 interactors by quantitative proteomics.
    J Proteome Res. 2014 Jun 6;13(6):3038-53 PMID: 24762188
  14. The mRNA-bound proteome of the early fly embryo.
    Genome Res. 2016 Jul;26(7):1000-9 PMID: 27197210
  15. The RNA-binding protein repertoire of embryonic stem cells.
    Nat Struct Mol Biol. 2013 Sep;20(9):1122-30 PMID: 23912277
  16. Examining the complexity of human RNA polymerase complexes using HaloTag technology coupled to label free quantitative proteomics.
    J Proteome Res. 2012 Feb 3;11(2):564-75 PMID: 22149079
  17. The BioPlex Network: A Systematic Exploration of the Human Interactome.
    Cell. 2015 Jul 16;162(2):425-40 PMID: 26186194
  18. RNA-binding proteins in Mendelian disease.
    Trends Genet. 2013 May;29(5):318-27 PMID: 23415593
  19. Rbfox proteins regulate alternative mRNA splicing through evolutionarily conserved RNA bridges.
    Nat Struct Mol Biol. 2013 Dec;20(12 ):1434-42 PMID: 24213538
  20. Global changes of the RNA-bound proteome during the maternal-to-zygotic transition in Drosophila.
    Nat Commun. 2016 Jul 05;7:12128 PMID: 27378189
  21. Promoter sequences direct cytoplasmic localization and translation of mRNAs during starvation in yeast.
    Nature. 2014 Oct 2;514(7520):117-21 PMID: 25119046
  22. Resources for the Comprehensive Discovery of Functional RNA Elements.
    Mol Cell. 2016 Mar 17;61(6):903-13 PMID: 26990993
  23. The RNA-binding proteomes from yeast to man harbour conserved enigmRBPs.
    Nat Commun. 2015 Dec 03;6:10127 PMID: 26632259
  24. Conserved mRNA-binding proteomes in eukaryotic organisms.
    Nat Struct Mol Biol. 2015 Dec;22(12):1027-33 PMID: 26595419
  25. Proteomic analysis by multidimensional protein identification technology.
    Methods Mol Biol. 2006;328:159-75 PMID: 16785648
  26. Endoplasmic reticulum stress-responsive transcription factor ATF6α directs recruitment of the Mediator of RNA polymerase II transcription and multiple histone acetyltransferase complexes.
    J Biol Chem. 2012 Jun 29;287(27):23035-45 PMID: 22577136
  27. Computational Prediction of RNA-Binding Proteins and Binding Sites.
    Int J Mol Sci. 2015 Nov 03;16(11):26303-17 PMID: 26540053
  28. Target Discrimination in Nonsense-Mediated mRNA Decay Requires Upf1 ATPase Activity.
    Mol Cell. 2015 Aug 6;59(3):413-25 PMID: 26253027
  29. The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts.
    Mol Cell. 2012 Jun 8;46(5):674-90 PMID: 22681889
  30. RNA-binding proteins: modular design for efficient function.
    Nat Rev Mol Cell Biol. 2007 Jun;8(6):479-90 PMID: 17473849
  31. A screen for RNA-binding proteins in yeast indicates dual functions for many enzymes.
    PLoS One. 2010 Nov 11;5(11):e15499 PMID: 21124907
  32. Integrative genome-wide analysis reveals cooperative regulation of alternative splicing by hnRNP proteins.
    Cell Rep. 2012 Feb 23;1(2):167-78 PMID: 22574288
  33. TRIM65 regulates microRNA activity by ubiquitination of TNRC6.
    Proc Natl Acad Sci U S A. 2014 May 13;111(19):6970-5 PMID: 24778252
  34. The C9orf72 repeat expansion disrupts nucleocytoplasmic transport.
    Nature. 2015 Sep 3;525(7567):56-61 PMID: 26308891
Article Info
Journal
Molecular cell
Abbr.
Mol Cell
ISSN
1097-4164
DOI
10.1016/j.molcel.2016.09.003
Email
[email protected]
Published
2016-00-20
Epub
2016-00-06
Pages
282-293
Language
English
Region
United States
NLM ID
9802571
PMCID
PMC5074894
Subset
IM
Grants
NHGRI NIH HHS · U54 HG007005 · United States
NHGRI NIH HHS · R01 HG004659 · United States
NCI NIH HHS · P30 CA023100 · United States
NIGMS NIH HHS · T32 GM008666 · United States
NINDS NIH HHS · R01 NS075449 · United States
External Links
PubMed source DOI: 10.1016/j.molcel.2016.09.003 PMC Full Text View journal details
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