SM-like proteins function in mRNA degradation of Saccharomyces cerevisiae

Persistent Link:
http://hdl.handle.net/10150/279964
Title:
SM-like proteins function in mRNA degradation of Saccharomyces cerevisiae
Author:
He, Weihai
Issue Date:
2001
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
The degradation of mRNA is a critical step in determining the regulation and levels of gene expression. A family of Sm-Like (Lsm) proteins containing the "Sm" sequence motif has been identified, which forms a complex with U6 snRNA and functions in pre-mRNA splicing. Moreover, Lsm proteins interact with mRNA decay factors in yeast two-hybrid analysis. One of the Lsm proteins, Lsm1p, is required for the efficient decapping of mRNA during degradation. Lsm proteins might exist as a complex since they coimmunoprecipitate with each other. Based on these observations we hypothesized that the family of Lsm proteins might be involved in mRNA degradation. We showed that mutations in seven Lsm proteins (Lsm1-Lsm7) caused inhibition of decapping. These Lsm proteins co-immunoprecipitated with Dcp1p (the decapping enzyme), Pat1p (a decapping activator) and with mRNA, indicating that the Lsm proteins (Lsm1--Lsm7) play a direct role in promoting the decapping step of mRNA degradation. In addition, the Lsm proteins seem to form distinct complexes that affect different aspects of mRNA metabolism. A nuclear Lsm complex consisting of Lsm2p through Lsm8p, interacts with U6 snRNA and promotes pre-mRNA splicing. A cytoplasmic Lsm complex consisting of Lsm1p through Lsm7p binds mRNA and functions in mRNA degradation. The cytoplasmic Lsm complex plays a second role in protecting the 3 ' UTR of mRNA from trimming. Mutations in the cytoplasmic Lsm complex caused trimming of mRNAs. The ski mutations, which cause defects in 3' to 5' mRNA degradation suppressed the temperature-sensitive growth of lsm mutants by preventing the further degradation of trimmed mRNAs. These results argue that Lsm complex might bind to the 3' UTR of mRNAs and protect it from trimming. In addition, the 3' to 5 ' degradation of the trimmed mRNAs might at least in part account for the temperature-sensitive growth of the lsm and the pat1 mutants.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Biology, Molecular.; Biology, Cell.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Molecular and Cellular Biology
Degree Grantor:
University of Arizona
Advisor:
Parker, Roy

Full metadata record

DC FieldValue Language
dc.language.isoen_USen_US
dc.titleSM-like proteins function in mRNA degradation of Saccharomyces cerevisiaeen_US
dc.creatorHe, Weihaien_US
dc.contributor.authorHe, Weihaien_US
dc.date.issued2001en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractThe degradation of mRNA is a critical step in determining the regulation and levels of gene expression. A family of Sm-Like (Lsm) proteins containing the "Sm" sequence motif has been identified, which forms a complex with U6 snRNA and functions in pre-mRNA splicing. Moreover, Lsm proteins interact with mRNA decay factors in yeast two-hybrid analysis. One of the Lsm proteins, Lsm1p, is required for the efficient decapping of mRNA during degradation. Lsm proteins might exist as a complex since they coimmunoprecipitate with each other. Based on these observations we hypothesized that the family of Lsm proteins might be involved in mRNA degradation. We showed that mutations in seven Lsm proteins (Lsm1-Lsm7) caused inhibition of decapping. These Lsm proteins co-immunoprecipitated with Dcp1p (the decapping enzyme), Pat1p (a decapping activator) and with mRNA, indicating that the Lsm proteins (Lsm1--Lsm7) play a direct role in promoting the decapping step of mRNA degradation. In addition, the Lsm proteins seem to form distinct complexes that affect different aspects of mRNA metabolism. A nuclear Lsm complex consisting of Lsm2p through Lsm8p, interacts with U6 snRNA and promotes pre-mRNA splicing. A cytoplasmic Lsm complex consisting of Lsm1p through Lsm7p binds mRNA and functions in mRNA degradation. The cytoplasmic Lsm complex plays a second role in protecting the 3 ' UTR of mRNA from trimming. Mutations in the cytoplasmic Lsm complex caused trimming of mRNAs. The ski mutations, which cause defects in 3' to 5' mRNA degradation suppressed the temperature-sensitive growth of lsm mutants by preventing the further degradation of trimmed mRNAs. These results argue that Lsm complex might bind to the 3' UTR of mRNAs and protect it from trimming. In addition, the 3' to 5 ' degradation of the trimmed mRNAs might at least in part account for the temperature-sensitive growth of the lsm and the pat1 mutants.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectBiology, Molecular.en_US
dc.subjectBiology, Cell.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplineMolecular and Cellular Biologyen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorParker, Royen_US
dc.identifier.proquest3010184en_US
dc.identifier.bibrecord.b41610933en_US
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