title: Discovering RNA-protein interactome by using chemical context profiling of the RNA-protein interface.
abstract: RNA-protein (RNP) interactions generally are required for RNA function. At least 5% of human genes code for RNA-binding proteins. Whereas many approaches can identify the RNA partners for a specific protein, finding the protein partners for a specific RNA is difficult. We present a machine-learning method that scores a protein's binding potential for an RNA structure by utilizing the chemical context profiles of the interface from known RNP structures. Our approach is applicable even when only a single RNP structure is available. We examined 801 mammalian proteins and find that 37 (4.6%) potentially bind transfer RNA (tRNA). Most are enzymes involved in cellular processes unrelated to translation and were not known to interact with RNA. We experimentally tested six positive and three negative predictions for tRNA binding in vivo, and all nine predictions were correct. Our computational approach provides a powerful complement to experiments in discovering new RNPs.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Parisien
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Wang
authors.forename: George
authors.initials: G
authors.lastname: Perdrizet
authors.forename: Corissa
authors.initials: C
authors.lastname: Lamphear
authors.forename: Carol A
authors.initials: CA
authors.lastname: Fierke
authors.forename: Ketan C
authors.initials: KC
authors.lastname: Maheshwari
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Wilde
authors.forename: Tobin R
authors.initials: TR
authors.lastname: Sosnick
authors.forename: Tao
authors.initials: T
authors.lastname: Pan
mesh_terms: D019295:Computational Biology; D030562:Databases, Protein; D057809:HEK293 Cells; D006801:Humans; D062105:Molecular Docking Simulation; D009690:Nucleic Acid Conformation; D059372:Nucleotide Motifs; D011485:Protein Binding; D012343:RNA, Transfer / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*
chemical_list: D016601:RNA-Binding Proteins; D012343:RNA, Transfer