Functional interactions between Prp8, Prp18, Slu7, and U5 snRNA during the second step of pre-mRNA splicing.

After the second transesterification step of pre-mRNA splicing, the Prp22 helicase catalyzes release of spliced mRNA by disrupting contacts in the spliceosome that likely involve Prp8. Mutations at Arg1753 in Prp8, which suppress helicase-defective prp22 mutants, elicit temperature-sensitive growth phenotypes, indicating that interactions in the spliceosome involving Prp8-R1753 might be ...
broken prematurely at 37 degrees C. Here we report that mutations in loop I of the U5 snRNA or in Prp18 can suppress the temperature-sensitive prp8-R1753 mutants. The same gain-of-function PRP18 alleles can also alleviate the growth phenotypes of multiple slu7-ts mutants, indicating a functional link between Prp8 and the second step splicing factors Prp18 and Slu7. These findings, together with the demonstration that changes at Arg1753 in Prp8 impair step 2 of pre-mRNA splicing in vitro, are consistent with a model in which (1) Arg1753 plays a role in stabilizing U5/exon interactions prior to exon joining and (2) these contacts persist until they are broken by the helicase Prp22.
Mesh Terms:
Cells, Cultured, Esterification, Exons, Humans, Nuclear Proteins, RNA Precursors, RNA Splicing, RNA, Fungal, RNA, Small Nuclear, Ribonucleoprotein, U4-U6 Small Nuclear, Ribonucleoprotein, U5 Small Nuclear, Ribonucleoproteins, Small Nuclear, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins
RNA
Date: Sep. 01, 2007
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