Reference: Frazer LN, et al. (2009) Analysis of synthetic lethality reveals genetic interactions between the GTPase Snu114p and snRNAs in the catalytic core of the Saccharomyces cerevisiae spliceosome. Genetics 183(2):497-515-1SI-4SI

Reference Help

Abstract


Conformational changes of snRNAs in the spliceosome required for pre-mRNA splicing are regulated by eight ATPases and one GTPase Snu114p. The Snu114p guanine state regulates U4/U6 unwinding during spliceosome activation and U2/U6 unwinding during spliceosome disassembly through the ATPase Brr2p. We investigated 618 genetic interactions to identify an extensive genetic interaction network between SNU114 and snRNAs. Snu114p G domain alleles were exacerbated by mutations that stabilize U4/U6 base pairing. G domain alleles were made worse by U2 and U6 mutations that stabilize or destabilize U2/U6 base pairing in helix I. Compensatory mutations that restored U2/U6 base pairing in helix I relieved synthetic lethality. Snu114p G domain alleles were also worsened by mutations in U6 predicted to increase 5' splice site base pairing. Both N-terminal and G domain alleles were exacerbated by U5 loop 1 mutations at positions involved in aligning exons while C-terminus alleles were synthetically lethal with U5 internal loop 1 mutations. This suggests a spatial orientation for Snu114p with U5. We propose that the RNA base pairing state is directly or indirectly sensed by the Snu114p G domain allowing the Snu114p C-terminal domain to regulate Brr2p or other proteins to bring about RNA/RNA rearrangements required for splicing.

Reference Type
Journal Article
Authors
Frazer LN, Lovell SC, O'Keefe RT
Primary Lit For
Additional Lit For
Review For

Interaction Annotations


Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.

Interactor Interactor Type Assay Annotation Action Modification Phenotype Source Reference

Gene Ontology Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Gene Gene Ontology Term Qualifier Aspect Method Evidence Source Assigned On Annotation Extension Reference

Phenotype Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details.

Gene Phenotype Experiment Type Mutant Information Strain Background Chemical Details Reference

Regulation Annotations


Increase the total number of rows displayed on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; to filter the table by a specific experiment type, type a keyword into the Filter box (for example, “microarray”); download this table as a .txt file using the Download button or click Analyze to further view and analyze the list of target genes using GO Term Finder, GO Slim Mapper, SPELL, or YeastMine.

Regulator Target Experiment Assay Construct Conditions Strain Background Reference