Identification and Characterization of Cytoplasmic Processing Bodies (P Bodies) in Saccharomyces Cerevisiae

Persistent Link:
http://hdl.handle.net/10150/194737
Title:
Identification and Characterization of Cytoplasmic Processing Bodies (P Bodies) in Saccharomyces Cerevisiae
Author:
Sheth, Ujwal
Issue Date:
2005
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:
An important aspect of regulating gene expression is the interplay between mRNA translation and its degradation. In the work presented here, I, in some cases in collaboration with others, provide insights into how mRNA translation and decay are connected and how they interact with each other to regulate gene expression. This work can be summarized as follows:First, I identified cytoplasmic processing bodies (P bodies) in yeast, which are sites where mRNAs can be decapped and degraded in a 5' to 3' manner. We base our conclusion on three key observations. First, factors involved in the 5' to 3' decay pathway accumulate in P bodies.Second, P bodies change in size when the flux of mRNA decay pathways is perturbed. For example, they decrease in size when entry into decapping is inhibited, and increase in size when decapping is blocked.Third, mRNAs trapped in the process of decay accumulate in P bodies. Second, in a collaborative effort, I have further characterized P bodies. This work involved addressing the role of RNA in P body formation and the relationship of P bodies to translation. Our results suggest that P bodies are dynamic and their size is affected by a range of cellular perturbations. We also provide evidence that P bodies are sensitive to the translational status of the cell and represent sites where translationally repressed mRNAs accumulate, and where they can be subjected to 5' to 3' decay. Third, I have determined that Nonsense-mediated decay (NMD), a quality control mechanism that rapidly degrades aberrant mRNAs, involves targeting of aberrant mRNAs to P bodies. In addition, I have identified specific roles for Upf proteins in the process of NMD: Upf1p is involved in targeting mRNAs to P bodies and Upf2p and Upf3p playing a role in degradation of the aberrant mRNAs within P bodies.The identification of P bodies has direct implications on regulation of mRNA decapping, of both normal and aberrant mRNAs. The similarities of P bodies with mRNA storage granules in other organisms imply that P bodies will play a major role in regulation of translationally repressed mRNAs.
Type:
text; Electronic Dissertation
Degree Name:
PhD
Degree Level:
doctoral
Degree Program:
Molecular & Cellular Biology; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Parker, Roy
Committee Chair:
Parker, Roy

Full metadata record

DC FieldValue Language
dc.language.isoENen_US
dc.titleIdentification and Characterization of Cytoplasmic Processing Bodies (P Bodies) in Saccharomyces Cerevisiaeen_US
dc.creatorSheth, Ujwalen_US
dc.contributor.authorSheth, Ujwalen_US
dc.date.issued2005en_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.abstractAn important aspect of regulating gene expression is the interplay between mRNA translation and its degradation. In the work presented here, I, in some cases in collaboration with others, provide insights into how mRNA translation and decay are connected and how they interact with each other to regulate gene expression. This work can be summarized as follows:First, I identified cytoplasmic processing bodies (P bodies) in yeast, which are sites where mRNAs can be decapped and degraded in a 5' to 3' manner. We base our conclusion on three key observations. First, factors involved in the 5' to 3' decay pathway accumulate in P bodies.Second, P bodies change in size when the flux of mRNA decay pathways is perturbed. For example, they decrease in size when entry into decapping is inhibited, and increase in size when decapping is blocked.Third, mRNAs trapped in the process of decay accumulate in P bodies. Second, in a collaborative effort, I have further characterized P bodies. This work involved addressing the role of RNA in P body formation and the relationship of P bodies to translation. Our results suggest that P bodies are dynamic and their size is affected by a range of cellular perturbations. We also provide evidence that P bodies are sensitive to the translational status of the cell and represent sites where translationally repressed mRNAs accumulate, and where they can be subjected to 5' to 3' decay. Third, I have determined that Nonsense-mediated decay (NMD), a quality control mechanism that rapidly degrades aberrant mRNAs, involves targeting of aberrant mRNAs to P bodies. In addition, I have identified specific roles for Upf proteins in the process of NMD: Upf1p is involved in targeting mRNAs to P bodies and Upf2p and Upf3p playing a role in degradation of the aberrant mRNAs within P bodies.The identification of P bodies has direct implications on regulation of mRNA decapping, of both normal and aberrant mRNAs. The similarities of P bodies with mRNA storage granules in other organisms imply that P bodies will play a major role in regulation of translationally repressed mRNAs.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
thesis.degree.namePhDen_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineMolecular & Cellular Biologyen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorParker, Royen_US
dc.contributor.chairParker, Royen_US
dc.contributor.committeememberVierling, Elizabethen_US
dc.contributor.committeememberDieckmann, Carolen_US
dc.contributor.committeememberFares, Hannaen_US
dc.contributor.committeememberWeinert, Teden_US
dc.identifier.proquest1353en_US
dc.identifier.oclc137355193en_US
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