title: Covariance analysis of RNA recognition motifs identifies functionally linked amino acids.
abstract: The RNA recognition motif (RRM) is one of the most common eukaryotic protein motifs. RRM sequences form a conserved globular structure known as the RNA-binding domain (RBD) or the ribonucleoprotein domain. Many proteins that contain RRM sequences bind RNA in a sequence-specific manner. To investigate the basis for the RNA-binding specificity of RRMs, we subjected 330 aligned RRM sequences to covariance analysis. The analysis revealed a single network of covariant amino acid pairs comprising the buried core of the RBD and a surface patch. Structural studies have implicated a subset of these residues in RNA binding. The covariance linkages identify a larger set of amino acid residues, including some not directly in contact with bound RNA, that may influence RNA-binding specificity.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3206, USA.
authors.forename: S
authors.initials: S
authors.lastname: Crowder
authors.forename: J
authors.initials: J
authors.lastname: Holton
authors.forename: T
authors.initials: T
authors.lastname: Alber
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D019295:Computational Biology; D017124:Conserved Sequence; D029721:Drosophila Proteins; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D013379:Substrate Specificity
chemical_list: D000596:Amino Acids; D029721:Drosophila Proteins; D016601:RNA-Binding Proteins; C067777:Sxl protein, Drosophila; D012313:RNA