Binding of the human Prp31 Nop domain to a composite RNA-protein platform in U4 snRNP.
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.
Liu
Sunbin
S
Abteilung Zelluläre Biochemie, Max-Planck-Institut für Biophysikalische Chemie, Am Fassberg 11, D-37077 Göttingen, Germany.
Li
Ping
P
Dybkov
Olexandr
O
Nottrott
Stephanie
S
Hartmuth
Klaus
K
Lührmann
Reinhard
R
Carlomagno
Teresa
T
Wahl
Markus C
MC
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
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