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Cwc21p promotes the second step conformation of the spliceosome and modulates 3' splice site selection.

ABSTRACT: Pre-mRNA splicing involves two transesterification steps catalyzed by the spliceosome. How RNA substrates are positioned in each step and the molecular rearrangements involved, remain obscure. Here, we show that mutations in PRP16, PRP8, SNU114 and the U5 snRNA that affect this process interact genetically with CWC21, that encodes the yeast orthologue of the human SR protein, SRm300/SRRM2. Our microarray analysis shows changes in 3' splice site selection at elevated temperature in a subset of introns in cwc21? cells. Considering all the available data, we propose a role for Cwc21p positioning the 3' splice site at the transition to the second step conformation of the spliceosome, mediated through its interactions with the U5 snRNP. This suggests a mechanism whereby SRm300/SRRM2, might influence splice site selection in human cells.

SUBMITTER: Gautam A

PROVIDER: S-EPMC4381068 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Cwc21p promotes the second step conformation of the spliceosome and modulates 3' splice site selection.

Gautam Amit A Grainger Richard J RJ Vilardell J J Barrass J David JD Beggs Jean D JD

Nucleic acids research 20150303 6

Pre-mRNA splicing involves two transesterification steps catalyzed by the spliceosome. How RNA substrates are positioned in each step and the molecular rearrangements involved, remain obscure. Here, we show that mutations in PRP16, PRP8, SNU114 and the U5 snRNA that affect this process interact genetically with CWC21, that encodes the yeast orthologue of the human SR protein, SRm300/SRRM2. Our microarray analysis shows changes in 3' splice site selection at elevated temperature in a subset of in ...[more]

PMID: 25740649

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