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An mRNA decapping mutant deficient in P body assembly limits mRNA stabilization in response to osmotic stress
Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). (Tracy Nissan)ORCID iD: 0000-0003-3956-7197
Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).ORCID iD: 0000-0003-0482-0543
2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, 44395Article in journal (Refereed) Published
Abstract [en]

Yeast is exposed to changing environmental conditions and must adapt its genetic program to provide a homeostatic intracellular environment. An important stress for yeast in the wild is high osmolarity. A key response to this stress is increased mRNA stability primarily by the inhibition of deadenylation. We previously demonstrated that mutations in decapping activators (edc3∆ lsm4∆C), which result in defects in P body assembly, can destabilize mRNA under unstressed conditions. We wished to examine whether mRNA would be destabilized in the edc3∆ lsm4∆C mutant as compared to the wild-type in response to osmotic stress, when P bodies are intense and numerous. Our results show that the edc3∆ lsm4∆C mutant limits the mRNA stability in response to osmotic stress, while the magnitude of stabilization was similar as compared to the wild-type. The reduced mRNA stability in the edc3∆ lsm4∆C mutant was correlated with a shorter PGK1 poly(A) tail. Similarly, the MFA2 mRNA was more rapidly deadenylated as well as significantly stabilized in the ccr4∆ deadenylation mutant in the edc3∆ lsm4∆C background. These results suggest a role for these decapping factors in stabilizing mRNA and may implicate P bodies as sites of reduced mRNA degradation.

Place, publisher, year, edition, pages
2017. Vol. 7, 44395
National Category
Biochemistry and Molecular Biology
Research subject
Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-132468DOI: 10.1038/srep44395ISI: 000396229600001OAI: oai:DiVA.org:umu-132468DiVA: diva2:1081720
Funder
Magnus Bergvall Foundation, 2016-01694Carl Tryggers foundation , 15:347Swedish Research Council, 621-2010-4602
Available from: 2017-03-14 Created: 2017-03-14 Last updated: 2017-05-12Bibliographically approved
In thesis
1. Spatial control of mRNA stability in yeast
Open this publication in new window or tab >>Spatial control of mRNA stability in yeast
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The degradation of mRNA is an important modulator of gene expression and the ultimate fate of messenger mRNA. Important steps in the degradation of mRNA include initial shortening of its poly(A) tail followed by the subsequent removal of the m7G cap. These two processes are linked temporally as well as spatially. In addition to physical interactions between proteins involved in these two processes, deadenylation and decapping enzymes and accessory factors are found in P bodies. P bodies are aggregates of protein and mRNA that are induced upon stress in all eukaryotes examined. In this thesis, I examine the spatial localization of decapping factors and explore the role of P bodies in mRNA turnover in the yeast Saccharomyces cerevisiae.  

This thesis is based on three underlying principles. First, mRNA decapping factors are membrane associated. More so, we show that decapping factors can be co-localized with the endoplasmic reticulum and Golgi apparatus. Second, although P bodies were proposed as sites of mRNA decay, we found that they stabilize mRNA. We examined the role of P bodies in mRNA turnover using a mutant defective in their assembly, edc3∆ lsm4∆C.  This strain is mutated in two decapping activators.  It combines a deletion of the gene encoding the Edc3 protein and lacks the prion-like domain of Lsm4. Using the edc3∆ lsm4∆C mutant, we demonstrate that mRNA stability is significantly reduced in the absence of P bodies for longer-lived mRNA. The effect of mRNA destabilization was due to increased deadenylation and decapping dependence. Finally, the decapping factor usually found in the cytoplasm, but accumulates in the nucleus in the P body deficient strain (edc3∆ lsm4∆C). This implies a possible role in modulating transcription.

A model for the functioning of P bodies that is consistent with our work is that P bodies serve a role as a cytoplasmic sink for degradation factors. By regulating the access of the cytosol to proteins involved in mRNA turnover, P bodies can modulate mRNA stability. This suggests a role for P bodies under stress and their potential importance in stress adaptation.

Place, publisher, year, edition, pages
Umeå: Umeå Universitet, 2017. 50 p.
Keyword
mRNA stability, P bodies, mRNA turnover, gene regulation, decapping factors
National Category
Biochemistry and Molecular Biology
Research subject
Molecular Biology
Identifiers
urn:nbn:se:umu:diva-133894 (URN)978-91-7601-721-0 (ISBN)
Public defence
2017-05-19, E04, Biomedicinehuset, Norrlands Universitetetssjukhus, Umeå, 09:00 (English)
Opponent
Supervisors
Funder
Swedish Research Council, 621-2010-4602
Available from: 2017-04-28 Created: 2017-04-20 Last updated: 2017-04-27Bibliographically approved

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