title: Binding of the human Prp31 Nop domain to a composite RNA-protein platform in U4 snRNP.
abstract: Although highly homologous, the spliceosomal hPrp31 and the nucleolar Nop56 and Nop58 (Nop56/58) proteins recognize different ribonucleoprotein (RNP) particles. hPrp31 interacts with complexes containing the 15.5K protein and U4 or U4atac small nuclear RNA (snRNA), whereas Nop56/58 associate with 15.5K-box C/D small nucleolar RNA complexes. We present structural and biochemical analyses of hPrp31-15.5K-U4 snRNA complexes that show how the conserved Nop domain in hPrp31 maintains high RNP binding selectivity despite relaxed RNA sequence requirements. The Nop domain is a genuine RNP binding module, exhibiting RNA and protein binding surfaces. Yeast two-hybrid analyses suggest a link between retinitis pigmentosa and an aberrant hPrp31-hPrp6 interaction that blocks U4/U6-U5 tri-snRNP formation.
authors.affiliation: Abteilung Zelluläre Biochemie, Max-Planck-Institut für Biophysikalische Chemie, Am Fassberg 11, D-37077 Göttingen, Germany.
authors.forename: Sunbin
authors.initials: S
authors.lastname: Liu
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Olexandr
authors.initials: O
authors.lastname: Dybkov
authors.forename: Stephanie
authors.initials: S
authors.lastname: Nottrott
authors.forename: Klaus
authors.initials: K
authors.lastname: Hartmuth
authors.forename: Reinhard
authors.initials: R
authors.lastname: Lührmann
authors.forename: Teresa
authors.initials: T
authors.lastname: Carlomagno
authors.forename: Markus C
authors.initials: MC
authors.lastname: Wahl
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D005136:Eye Proteins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D000072260:RNA Splicing Factors; D012342:RNA, Small Nuclear / Q000737:chemistry* / Q000378:metabolism*; D016601:RNA-Binding Proteins; D012174:Retinitis Pigmentosa / Q000235:genetics; D017414:Ribonucleoprotein, U4-U6 Small Nuclear / Q000737:chemistry* / Q000378:metabolism*; D014157:Transcription Factors
chemical_list: D002352:Carrier Proteins; D005136:Eye Proteins; C454222:PRPF31 protein, human; C408605:PRPF6 protein, human; D000072260:RNA Splicing Factors; D012342:RNA, Small Nuclear; D016601:RNA-Binding Proteins; D017414:Ribonucleoprotein, U4-U6 Small Nuclear; D014157:Transcription Factors; C405482:U4 small nuclear RNA