Discovering novel roles for the RNA binding protein Whi3 during stress

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Abstract/Contents

Abstract
Whi3 is an RNA binding protein that regulates cell cycle entry by binding to mRNA of the G1 cyclin CLN3 and to the cyclin-dependent kinase Cdc28. Cln3 binds to Cdc28 to promote passage through Start. whi3[delta] cells have a small size phenotype, and Whi3 may regulate cell size by sequestering CLN3 mRNA and Cdc28 protein in the cytoplasm to delay G1 entry (Wang et al., 2004). We observe that Whi3 reversibly localizes from the cytosol to cytoplasmic puncta in response to glucose deprivation and heat shock. This phenotype is shared by components of stress granules (SGs), which are large RNP complexes that form in yeast in response to various stress conditions; SGs sort and process mRNAs during the stress response (Buchan et al., 2008). Because Whi3 shares several characteristics with known SG components, including an RNA binding domain and stress-dependent relocalization, we hypothesize that Whi3 is a novel component of SGs. We show that Whi3 colocalizes with SG markers in response to glucose deprivation and heat shock. Preventing SG formation inhibits Whi3 foci formation. Like SG components, Whi3 is enriched in insoluble cell fractions during stress. Whi3 is not required for SG formation, but may be targeted to SGs to carry out a previously unknown function. We conclude that Whi3 is a novel component of yeast stress granules. This observation suggests an alternative model for Whi3 function: that Whi3 might regulate mRNA translation during stress by transporting mRNA to stress granules. We demonstrate that Whi3 regulates many of its interacting RNAs, and that this regulation may promote stress-dependent survival.

Description

Type of resource text
Form electronic; electronic resource; remote
Extent 1 online resource.
Publication date 2012
Issuance monographic
Language English

Creators/Contributors

Associated with Holmes, Kristen Jones
Associated with Stanford University, Department of Biology.
Primary advisor Cyert, Martha S, 1958-
Thesis advisor Cyert, Martha S, 1958-
Thesis advisor Sarnow, P. (Peter)
Thesis advisor Simon, Michael, (Biology professor)
Thesis advisor Skotheim, Jan, 1977-
Advisor Sarnow, P. (Peter)
Advisor Simon, Michael, (Biology professor)
Advisor Skotheim, Jan, 1977-

Subjects

Genre Theses

Bibliographic information

Statement of responsibility Kristen Jones Holmes.
Note Submitted to the Department of Biological Sciences.
Thesis Ph.D. Stanford University 2012
Location electronic resource

Access conditions

Copyright
© 2012 by Kristen Jones Holmes
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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