Premium
Investigation of the Role of the Proteasomal Subunit Rpn10 in pre‐mRNA Splicing
Author(s) -
Merkhofer Evan C,
Johnson Tracy
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.743.1
Subject(s) - spliceosome , rna splicing , biology , genetics , microbiology and biotechnology , protein subunit , polypyrimidine tract , exonic splicing enhancer , ribonucleoprotein , alternative splicing , gene , rna , messenger rna
The removal of non‐coding sequences from protein‐coding pre‐messenger RNAs is required for proper gene expression. This highly conserved process, commonly known as RNA splicing, is mediated by a large ribonucleoprotein complex known as the spliceosome. Dysregulation of RNA splicing is common in disease, as up to 15% of mutations leading to disease have been attributed to an effect on pre‐mRNA splicing. The DExD/H‐box family of ATPases, including Prp5, play a critical role in mediating ATP‐dependent RNA remodeling in splicing. One pressing question that remains is what factors are required for rapid ATP‐dependent rearrangements of the spliceosome that underlie high fidelity splice site recognition. Using Saccharomyces cerevisiae , our studies of the mechanisms of spliceosomal rearrangements have identified striking genetic interactions between the Rpn10 subunit of the proteasome and the ATP‐dependent spliceosomal RNPase Prp5. Deletion of rpn10 rescues the slow growth phenotype exhibited by strains containing prp5 ATPase mutations, and leads to an increase in splicing in vitro . Furthermore, we show that Rpn10 can regulate protein levels of multiple spliceosome components, including Cus2, and rpn10 shows strong genetic interactions with this gene. These intriguing results suggest a novel role of the regulatory subunit of the proteasome in mediating rearrangements between components of the spliceosome.