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PMID: 16885028 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

The EF-G-like GTPase Snu114p regulates spliceosome dynamics mediated by Brr2p, a DExD/H box ATPase.

Molecular cell ·Vol. 23 ·No. 3 ·2006-08-04 ·Pages 389-99

Small EC, Leggett SR, Winans AA, Staley JP

Abstract

Binding of a pre-mRNA substrate triggers spliceosome activation, whereas the release of the mRNA product triggers spliceosome disassembly. The mechanisms that underlie the regulation of these rearrangements remain unclear. We find evidence that the GTPase Snu114p mediates the regulation of spliceosome activation and disassembly. Specifically, both unwinding of U4/U6, required for spliceosome activation, and disassembly of the postsplicing U2/U6.U5.intron complex are repressed by Snu114p bound to GDP and derepressed by Snu114p bound to GTP or nonhydrolyzable GTP analogs. Further, similar to U4/U6 unwinding, spliceosome disassembly requires the DExD/H box ATPase Brr2p. Together, our data define a common mechanism for regulating and executing spliceosome activation and disassembly. Although sequence similarity with EF-G suggests Snu114p functions as a molecular motor, our findings indicate that Snu114p functions as a classic regulatory G protein. We propose that Snu114p serves as a signal-dependent switch that transduces signals to Brr2p to control spliceosome dynamics.

MeSH Terms
Adenosine Triphosphate/metabolism,pharmacology DEAD-box RNA Helicases Guanosine Diphosphate/metabolism,pharmacology Guanosine Triphosphate/metabolism,pharmacology Introns/genetics Models, Biological Mutation/genetics Nucleic Acid Conformation/drug effects RNA Helicases/analysis RNA Nucleotidyltransferases/analysis RNA Precursors/metabolism RNA Splicing/genetics RNA Splicing Factors RNA, Small Nuclear/analysis,chemistry,metabolism Repressor Proteins/genetics,physiology Ribonucleoprotein, U5 Small Nuclear/genetics,physiology Ribonucleotides/pharmacology Saccharomyces cerevisiae/genetics,physiology Saccharomyces cerevisiae Proteins/analysis,genetics,physiology Spliceosomes/chemistry,drug effects,metabolism
Chemicals
RNA Precursors RNA Splicing Factors RNA, Small Nuclear Repressor Proteins Ribonucleoprotein, U5 Small Nuclear Ribonucleotides SNU114 protein, S cerevisiae Saccharomyces cerevisiae Proteins U2 small nuclear RNA U5 small nuclear RNA U6 small nuclear RNA Guanosine Diphosphate xanthosine 5'-triphosphate Guanosine Triphosphate Adenosine Triphosphate RNA Nucleotidyltransferases BRR2 protein, S cerevisiae PRP22 protein, S cerevisiae PRP28 protein, S cerevisiae PRP43 protein, S cerevisiae DEAD-box RNA Helicases RNA Helicases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Small Eliza C
Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, Illinois 60637, USA.
Leggett Stephanie R
Winans Adrienne A
Staley Jonathan P
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Article Info
Journal
Molecular cell
Abbr.
Mol Cell
ISSN
1097-2765
DOI
10.1016/j.molcel.2006.05.043
Published
2006-08-04
Pages
389-99
Language
English
Region
United States
NLM ID
9802571
PMCID
PMC3777414
Subset
IM
Grants
NIGMS NIH HHS · R01 GM062264 · United States
NIGMS NIH HHS · T32 GM007183 · United States
NIGMS NIH HHS · GM62264 · United States
External Links
PubMed source DOI: 10.1016/j.molcel.2006.05.043 PMC Full Text View journal details
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