title: Comprehensive Identification of RNA-Binding Domains in Human Cells.
abstract: Mammalian cells harbor more than a thousand RNA-binding proteins (RBPs), with half of these employing unknown modes of RNA binding. We developed RBDmap to determine the RNA-binding sites of native RBPs on a proteome-wide scale. We identified 1,174 binding sites within 529 HeLa cell RBPs, discovering numerous RNA-binding domains (RBDs). Catalytic centers or protein-protein interaction domains are in close relationship with RNA-binding sites, invoking possible effector roles of RNA in the control of protein function. Nearly half of the RNA-binding sites map to intrinsically disordered regions, uncovering unstructured domains as prevalent partners in protein-RNA interactions. RNA-binding sites represent hot spots for defined posttranslational modifications such as lysine acetylation and tyrosine phosphorylation, suggesting metabolic and signal-dependent regulation of RBP function. RBDs display a high degree of evolutionary conservation and incidence of Mendelian mutations, suggestive of important functional roles. RBDmap thus yields profound insights into native protein-RNA interactions in living cells.
authors.affiliation: European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany; Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Castello
authors.affiliation: European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany; German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Fischer
authors.affiliation: European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Christian K
authors.initials: CK
authors.lastname: Frese
authors.affiliation: European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Rastislav
authors.initials: R
authors.lastname: Horos
authors.affiliation: European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Alleaume
authors.affiliation: European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany.
authors.forename: Sophia
authors.initials: S
authors.lastname: Foehr
authors.affiliation: European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany; Faculty of Computer and Information Science, University of Ljubljana, 1001 Ljubljana, Slovenia.
authors.forename: Tomaz
authors.initials: T
authors.lastname: Curk
authors.affiliation: European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany; German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Krijgsveld
authors.affiliation: European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany. Electronic address: hentze@embl.de.
authors.forename: Matthias W
authors.initials: MW
authors.lastname: Hentze
mesh_terms: D000107:Acetylation; D019295:Computational Biology; D030562:Databases, Protein; D019143:Evolution, Molecular; D006367:HeLa Cells; D006801:Humans; D008745:Methylation; D008958:Models, Molecular; D009154:Mutation; D009690:Nucleic Acid Conformation; D010766:Phosphorylation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D011499:Protein Processing, Post-Translational; D040901:Proteomics / Q000379:methods*; D012313:RNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000071376:RNA-Binding Motifs; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D016601:RNA-Binding Proteins; D012313:RNA