Binding of the human Prp31 Nop domain to a composite RNA-protein platform in U4 snRNP

Science. 2007 Apr 6;316(5821):115-20. doi: 10.1126/science.1137924.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Amino Acid Substitution
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism
  • Eye Proteins / chemistry*
  • Eye Proteins / metabolism*
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Nucleic Acid Conformation
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • RNA Splicing Factors
  • RNA, Small Nuclear / chemistry*
  • RNA, Small Nuclear / metabolism*
  • RNA-Binding Proteins
  • Retinitis Pigmentosa / genetics
  • Ribonucleoprotein, U4-U6 Small Nuclear / chemistry*
  • Ribonucleoprotein, U4-U6 Small Nuclear / metabolism*
  • Transcription Factors

Substances

  • Carrier Proteins
  • Eye Proteins
  • PRPF31 protein, human
  • PRPF6 protein, human
  • RNA Splicing Factors
  • RNA, Small Nuclear
  • RNA-Binding Proteins
  • Ribonucleoprotein, U4-U6 Small Nuclear
  • Transcription Factors
  • U4 small nuclear RNA