title: The testis-specific human protein RBMY recognizes RNA through a novel mode of interaction.
abstract: The RBMY (RNA-binding motif gene on Y chromosome) protein encoded by the human Y chromosome is important for normal sperm development. Although its precise molecular RNA targets are unknown at present, it is suggested that human RBMY (hRBMY) participates in splicing in the testis. Using systematic evolution of ligands by exponential enrichment, we found that RNA stem-loops capped by a C(A)/(U)CAA pentaloop are high-affinity binding targets for hRBMY. Subsequent nuclear magnetic resonance structural determination of the hRBMY RNA recognition motif (RRM) in complex with a high-affinity target showed two distinct modes of RNA recognition. First, the RRM beta-sheet surface binds to the RNA loop in a sequence-specific fashion. Second, the beta2-beta3 loop of the hRBMY inserts into the major groove of the RNA stem. The first binding mode might be conserved in the paralogous protein heterogeneous nuclear RNP G, whereas the second mode of binding is found only in hRBMY. This structural difference could be at the origin of the function of RBMY in spermatogenesis.
authors.affiliation: Institute of Molecular Biology and Biophysics, ETH Zurich, Swiss Federal Institute of Technology, 8093 Zurich, Switzerland.
authors.forename: Lenka
authors.initials: L
authors.lastname: Skrisovska
authors.forename: Cyril F
authors.initials: CF
authors.lastname: Bourgeois
authors.forename: Richard
authors.initials: R
authors.lastname: Stefl
authors.forename: Sushma-Nagaraja
authors.initials: SN
authors.lastname: Grellscheid
authors.forename: Liliane
authors.initials: L
authors.lastname: Kister
authors.forename: Philipp
authors.initials: P
authors.lastname: Wenter
authors.forename: David J
authors.initials: DJ
authors.lastname: Elliott
authors.forename: James
authors.initials: J
authors.lastname: Stevenin
authors.forename: Frédéric H-T
authors.initials: FH
authors.lastname: Allain
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019020:Directed Molecular Evolution; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017433:Protein Structure, Secondary; D012313:RNA / Q000737:chemistry* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D052156:SELEX Aptamer Technique; D020539:Sequence Analysis, Protein; D013737:Testis / Q000378:metabolism*
chemical_list: D009687:Nuclear Proteins; C501499:RBMY1A1 protein, human; D016601:RNA-Binding Proteins; D012313:RNA