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- Title
A role for ubiquitin in the spliceosome assembly pathway.
- Authors
Bellare, Priya; Small, Eliza C; Huang, Xinhua; Wohlschlegel, James A; Staley, Jonathan P; Sontheimer, Erik J
- Abstract
The spliceosome uses numerous strategies to regulate its function in mRNA maturation. Ubiquitin regulates many cellular processes, but its potential roles during splicing are unknown. We have developed a new strategy that reveals a direct role for ubiquitin in the dynamics of splicing complexes. A ubiquitin mutant (I44A) that can enter the conjugation pathway but is compromised in downstream functions diminishes splicing activity by reducing the levels of the U4/U6-U5 small nuclear ribonucleoprotein (snRNP). Similarly, an inhibitor of ubiquitin's protein-protein interactions, ubistatin A, reduces U4/U6-U5 triple snRNP levels in vitro. When ubiquitin interactions are blocked, ATP-dependent disassembly of purified U4/U6-U5 particles is accelerated, indicating a direct role for ubiquitin in repressing U4/U6 unwinding. Finally, we show that the conserved splicing factor Prp8 is ubiquitinated within purified triple snRNPs. These results reveal a previously unknown ubiquitin-dependent mechanism for controlling the pre-mRNA splicing pathway.
- Publication
Nature structural & molecular biology, 2008, Vol 15, Issue 5, p444
- ISSN
1545-9985
- Publication type
Journal Article
- DOI
10.1038/nsmb.1401