A Role for Ubiquitin in the Spliceosome Assembly Pathway

Overview

Journal Nat Struct Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2008 Apr 22

PMID 18425143

Citations 76

Authors

Priya Bellare

Eliza C Small

Xinhua Huang

James A Wohlschlegel

Jonathan P Staley

Erik J Sontheimer

Affiliations

Soon will be listed here.

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.

Citing Articles

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