STM1 IS A NOVEL REGULATOR OF MESSENGER RNA TRANSLATION AND DEGRADATION IN SACCHAROMYCES CEREVISIAE

Persistent Link:
http://hdl.handle.net/10150/145717
Title:
STM1 IS A NOVEL REGULATOR OF MESSENGER RNA TRANSLATION AND DEGRADATION IN SACCHAROMYCES CEREVISIAE
Author:
Balagopal, Vidya
Issue Date:
2010
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.
Embargo:
Embargo: Release after 7/9/2010
Abstract:
In eukaryotes, regulation of translation and decay of messenger RNA are critical for fine-tuned control of gene expression. An important point of control is the key transition where mRNAs exit translation and assemble into a non-translating mRNP state that can accumulate in cytoplasmic granules such as P bodies and/or Stress granules. In the budding yeast Saccharomyces cerevisiae , the activators of decapping Dhh1 and Pat1 appear to promote the exit of mRNAs from translation. In my work, summarized below, I describe a new regulator of translation repression and mRNA degradation, Stm1, and its novel mode of action. First, I identified Stm1 as a novel regulator of translation repression and mRNA decay. Stm1 shows several genetic interactions with Pat1 and Dhh1, in a manner consistent with Stm1 promoting the function of Dhh1. This suggests that Stm1 has a role to play in translation repression and/or activation of mRNA decay. stm1 δ strains are defective in the degradation of a subset of mRNAs that include EDC1 and COX17 . These results strongly argue that Stm1 is a novel addition to the mRNA degradation machinery. Second, I have shown that Stm1, a known ribosome-associated protein, can bind and stall 80S ribosomes to repress translation and promote decay. Stm1 is able to repress translation and stall an 80S complex in vitro . Several mutations were identified in the protein, which link the in vitrophenotype to its biological functionin vivo. The analysis of different steps in translation reveals Stm1 functions in a novel manner to inhibit translation after the formation of an 80S complex. Since most of the regulation of translation is thought to happen at the stage of initiation, this study reveals a novel mode of translation regulation. These results also provide a direct and mechanistic link between ribosome function, inhibition of translation and the degradation of messenger RNAs.
Type:
text; Electronic Dissertation
Keywords:
Dhh1; mRNA decay; Ribosome; Stm1; Translation
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Molecular & Cellular Biology
Degree Grantor:
University of Arizona
Advisor:
Parker, Roy

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleSTM1 IS A NOVEL REGULATOR OF MESSENGER RNA TRANSLATION AND DEGRADATION IN SACCHAROMYCES CEREVISIAEen_US
dc.creatorBalagopal, Vidyaen_US
dc.contributor.authorBalagopal, Vidyaen_US
dc.date.issued2010-
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.releaseEmbargo: Release after 7/9/2010en_US
dc.description.abstractIn eukaryotes, regulation of translation and decay of messenger RNA are critical for fine-tuned control of gene expression. An important point of control is the key transition where mRNAs exit translation and assemble into a non-translating mRNP state that can accumulate in cytoplasmic granules such as P bodies and/or Stress granules. In the budding yeast Saccharomyces cerevisiae , the activators of decapping Dhh1 and Pat1 appear to promote the exit of mRNAs from translation. In my work, summarized below, I describe a new regulator of translation repression and mRNA degradation, Stm1, and its novel mode of action. First, I identified Stm1 as a novel regulator of translation repression and mRNA decay. Stm1 shows several genetic interactions with Pat1 and Dhh1, in a manner consistent with Stm1 promoting the function of Dhh1. This suggests that Stm1 has a role to play in translation repression and/or activation of mRNA decay. stm1 δ strains are defective in the degradation of a subset of mRNAs that include EDC1 and COX17 . These results strongly argue that Stm1 is a novel addition to the mRNA degradation machinery. Second, I have shown that Stm1, a known ribosome-associated protein, can bind and stall 80S ribosomes to repress translation and promote decay. Stm1 is able to repress translation and stall an 80S complex in vitro . Several mutations were identified in the protein, which link the in vitrophenotype to its biological functionin vivo. The analysis of different steps in translation reveals Stm1 functions in a novel manner to inhibit translation after the formation of an 80S complex. Since most of the regulation of translation is thought to happen at the stage of initiation, this study reveals a novel mode of translation regulation. These results also provide a direct and mechanistic link between ribosome function, inhibition of translation and the degradation of messenger RNAs.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjectDhh1en_US
dc.subjectmRNA decayen_US
dc.subjectRibosomeen_US
dc.subjectStm1en_US
dc.subjectTranslationen_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplineMolecular & Cellular Biologyen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorParker, Royen_US
dc.contributor.committeememberDieckmann, Carolen_US
dc.contributor.committeememberFares, Hannaen_US
dc.contributor.committeememberWeinert, Teden_US
dc.contributor.committeememberWard, Samuelen_US
dc.identifier.proquest11205-
dc.identifier.oclc752261051-
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