Abstract
U4 and U6 small nuclear RNAs are associated by an extensive base-pairing interaction that must be disrupted and reformed with each round of splicing. U4 mutations within the U4/U6 interaction domain destabilize the complex in vitro and cause a cold-sensitive phenotype in vivo. Restabilization of the U4/U6 helix by dominant (gain-of-function), compensatory mutations in U6 results in wild-type growth. Cold-insensitive growth can also be restored by two classes of recessive (loss-of-function) suppressors: (1) mutations in PRP24, which we show to be a U6-specific binding protein of the RNP-consensus family; and (2) mutations in U6, which lie outside the interaction domain and identify putative PRP24-binding sites. Destabilization of the U4/U6 helix causes the accumulation of a PRP24/U4/U6 complex, which is undetectable in wild-type cells. The loss-of-function suppressor mutations inhibit the binding of PRP24 to U6, and thus presumably promote the release of PRP24 from the PRP24/U4/U6 complex and the reformation of the base-paired U4/U6 snRNP. We propose that the PRP24/U4/U6 complex is normally a highly transient intermediate in the spliceosome cycle and that PRP24 promotes the reannealing of U6 with U4.
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Dates
Type | When |
---|---|
Created | 18 years, 2 months ago (June 5, 2007, 5:15 p.m.) |
Deposited | 3 years, 9 months ago (Nov. 13, 2021, 11:18 p.m.) |
Indexed | 2 weeks, 5 days ago (Aug. 6, 2025, 8:54 a.m.) |
Issued | 34 years, 3 months ago (May 1, 1991) |
Published | 34 years, 3 months ago (May 1, 1991) |
Published Online | 34 years, 3 months ago (May 1, 1991) |
Published Print | 34 years, 3 months ago (May 1, 1991) |
@article{Shannon_1991, title={Suppressors of a U4 snRNA mutation define a novel U6 snRNP protein with RNA-binding motifs.}, volume={5}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.5.5.773}, DOI={10.1101/gad.5.5.773}, number={5}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Shannon, K W and Guthrie, C}, year={1991}, month=may, pages={773–785} }