Trans-acting factors and cis-acting sequences in posttranscriptional gene expression

Persistent Link:
http://hdl.handle.net/10150/284109
Title:
Trans-acting factors and cis-acting sequences in posttranscriptional gene expression
Author:
Jacobs Anderson, John Stephen
Issue Date:
2000
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 control of gene expression is greatly influenced by regulatory events at post-transcriptional steps. In my studies of these post-transcriptional control steps, I have utilized the tools provided by the model organism Saccharomyces cerevisiae, including genetic and molecular tools as well as the complete genome sequence. Based on genetic evidence, I hypothesized that the products of the SKI2, SKI3, and SKI8 genes were involved in a pathway of mRNA degradation that acts in the 3' to 5' direction. I demonstrated that mutations in any of the three genes lead to a stabilization of an mRNA species that degrades 3' to 5'. I further demonstrated that components of a protein complex, the exosome, were also required for 3' to 5 ' mRNA degradation. I went on to demonstrate that mutations that disrupt 3' to 5' mRNA degradation are synthetically lethal with mutations that disrupt another pathway that operates in the 5' to 3' direction. This last observation leads to two conclusions. First, these two mechanisms are likely to be the only major methods of mRNA degradation in Saccharomyces cerevisiae. Second, mRNA degradation is an essential process in this organism. I developed a computational method that uses statistical analysis of oligonucleotide frequencies to identify potential cis-acting elements. Application of my method to a group of genes allows the identification of sequences that may be involved in directing co-regulation. Unlike similar methods, my method accounts for oligonucleotide usage in the genes that are not observed to be co-regulated, ensuring that elements common to all genes will not be erroneously detected. After demonstrating that the method detected several known splicing elements in a group of genes containing introns, I went on to characterize the performance of the method under several conditions designed to simulate 'real world' experiments. Finally, I utilized the method to identify an element in a group of nuclear genes that encode mitochondrial proteins.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Biology, Molecular.; Biology, Microbiology.
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.titleTrans-acting factors and cis-acting sequences in posttranscriptional gene expressionen_US
dc.creatorJacobs Anderson, John Stephenen_US
dc.contributor.authorJacobs Anderson, John Stephenen_US
dc.date.issued2000en_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 control of gene expression is greatly influenced by regulatory events at post-transcriptional steps. In my studies of these post-transcriptional control steps, I have utilized the tools provided by the model organism Saccharomyces cerevisiae, including genetic and molecular tools as well as the complete genome sequence. Based on genetic evidence, I hypothesized that the products of the SKI2, SKI3, and SKI8 genes were involved in a pathway of mRNA degradation that acts in the 3' to 5' direction. I demonstrated that mutations in any of the three genes lead to a stabilization of an mRNA species that degrades 3' to 5'. I further demonstrated that components of a protein complex, the exosome, were also required for 3' to 5 ' mRNA degradation. I went on to demonstrate that mutations that disrupt 3' to 5' mRNA degradation are synthetically lethal with mutations that disrupt another pathway that operates in the 5' to 3' direction. This last observation leads to two conclusions. First, these two mechanisms are likely to be the only major methods of mRNA degradation in Saccharomyces cerevisiae. Second, mRNA degradation is an essential process in this organism. I developed a computational method that uses statistical analysis of oligonucleotide frequencies to identify potential cis-acting elements. Application of my method to a group of genes allows the identification of sequences that may be involved in directing co-regulation. Unlike similar methods, my method accounts for oligonucleotide usage in the genes that are not observed to be co-regulated, ensuring that elements common to all genes will not be erroneously detected. After demonstrating that the method detected several known splicing elements in a group of genes containing introns, I went on to characterize the performance of the method under several conditions designed to simulate 'real world' experiments. Finally, I utilized the method to identify an element in a group of nuclear genes that encode mitochondrial proteins.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectBiology, Molecular.en_US
dc.subjectBiology, Microbiology.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.proquest9965896en_US
dc.identifier.bibrecord.b40480859en_US
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