Ubiquitin binding by a variant Jab1/MPN domain in the essential pre-mRNA splicing factor Prp8p.
The U1, U2, U4/U6, and U5 small nuclear ribonucleoproteins (snRNPs) are components of the spliceosome, which catalyzes pre-mRNA splicing. One of the largest and the most highly conserved proteins in the spliceosome is Prp8p, a component of the U5 snRNP. Despite its size and conservation, very few motifs have been identified that suggest specific biochemical functions. A variant of the Jab1/MPN domain found in a class of deubiquitinating enzymes is present near the C terminus of Prp8p. Ubiquitination regulates a broad range of cellular pathways, and its functions generally require ubiquitin recognition by one or more ubiquitin-binding domains (UBDs). No precise role for ubiquitin has been defined in the pre-mRNA splicing pathway, and no known UBDs have been found within splicing proteins. Here we show that a Prp8p fragment containing the Jab1/MPN domain binds directly to ubiquitin with an affinity comparable to other known UBDs. Several mutations within this domain that compromise splicing also reduce interaction of the fragment with ubiquitin-Sepharose. Our results define a new UBD and suggest functional links between ubiquitin and the pre-mRNA splicing machinery.
Pubmed ID: 16428608 RIS Download
Amino Acid Motifs | Amino Acid Sequence | Binding Sites | Gene Expression Regulation, Fungal | Metalloendopeptidases | Molecular Sequence Data | Mutation | Protein Structure, Tertiary | RNA Precursors | RNA Splicing | Ribonucleoprotein, U4-U6 Small Nuclear | Ribonucleoprotein, U5 Small Nuclear | Saccharomyces cerevisiae Proteins | Sequence Homology, Amino Acid | Ubiquitin