Description:
<jats:p>Recent studies have shown that pre‐mRNA splicing occurs co‐transcriptionally. The next key challenge is to identify specific factors that coordinate pre‐mRNA splicing with transcription, particularly within the context of a chromatin template. We have previously shown that Gcn5, which encodes the HAT activity of the co‐activator SAGA complex, mediates co‐transcriptional recruitment of the U2 snRNP to pre‐mRNA. As further evidence of a role for SAGA in mediating ATP‐dependent rearrangement of the U2 snRNP, we have identified interactions between the DExH/D box protein Prp5, which hydrolyzes ATP to remodel the U2 snRNP and facilitate branchpoint recognition, and components of SAGA. A lethal mutation in PRP5 that eliminates ATP‐binding is suppressed when components of the SAGA complex are deleted, thereby for the first time linking SAGA with a catalytic activity that drives spliceosomal rearrangements. These results have led us to further analyze how histone acetylation contributes to U2 snRNP recruitment. We find that chromatin remodeling complexes that associate with acetylated histones physically and functionally interact with the U2 snRNP and contribute to spliceosome assembly. These data support a model whereby co‐transcriptional spliceosome assembly is intimately coordinated with histone acetylation and chromatin remodeling. Support: NSF CAREER MCB0448010 and NIGMS <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="DDBJ/EMBL/GenBank" xlink:href="GM085474">GM085474</jats:ext-link>; GM085764.</jats:p>