title: SONAR Discovers RNA-Binding Proteins from Analysis of Large-Scale Protein-Protein Interactomes.
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.
authors.affiliation: Department of Cellular and Molecular Medicine, Stem Cell Program and Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Kristopher W
authors.initials: KW
authors.lastname: Brannan
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 117597 Singapore, Singapore.
authors.forename: Wenhao
authors.initials: W
authors.lastname: Jin
authors.affiliation: Department of Cellular and Molecular Medicine, Stem Cell Program and Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Huelga
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
authors.forename: Charles A S
authors.initials: CA
authors.lastname: Banks
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Gilmore
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
authors.forename: Laurence
authors.initials: L
authors.lastname: Florens
authors.affiliation: 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.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Washburn
authors.affiliation: Department of Cellular and Molecular Medicine, Stem Cell Program and Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Eric L
authors.initials: EL
authors.lastname: Van Nostrand
authors.affiliation: Department of Cellular and Molecular Medicine, Stem Cell Program and Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Gabriel A
authors.initials: GA
authors.lastname: Pratt
authors.affiliation: Promega Corporation, 2800 Woods Hollow Road, Madison, WI 53711, USA.
authors.forename: Marie K
authors.initials: MK
authors.lastname: Schwinn
authors.affiliation: Promega Corporation, 2800 Woods Hollow Road, Madison, WI 53711, USA.
authors.forename: Danette L
authors.initials: DL
authors.lastname: Daniels
authors.affiliation: 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: geneyeo@ucsd.edu.
authors.forename: Gene W
authors.initials: GW
authors.lastname: Yeo
mesh_terms: D000465:Algorithms; D000818:Animals; D001665:Binding Sites; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D063990:Gene Ontology; D057809:HEK293 Cells; D006801:Humans; D058977:Molecular Sequence Annotation; D059372:Nucleotide Motifs; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D012313:RNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000145:classification* / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D012984:Software; D016335:Zinc Fingers
chemical_list: D016601:RNA-Binding Proteins; D012313:RNA
keywords: RNA-binding proteins; machine-learning; protein-protein interaction networks; support vector machine