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Rph1 functions downstream of TOR and Rim15 in yeast but is not needed for chronological lifespan extension
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Sveriges lantbruksuniversitet, fakulteten för naturresurser och lantbruksvetenskap, institutionen för mikrobiologi.
Sveriges lantbruksuniversitet, fakulteten för naturresurser och lantbruksvetenskap, institutionen för mikrobiologi.
Sveriges lantbruksuniversitet, fakulteten för naturresurser och lantbruksvetenskap, institutionen för mikrobiologi.
(English)Manuscript (preprint) (Other academic)
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:uu:diva-173014OAI: oai:DiVA.org:uu-173014DiVA: diva2:516488
Available from: 2012-04-18 Created: 2012-04-17 Last updated: 2012-08-01
In thesis
1. Studies of Budding Yeast Transcription Factors Acting Downstream of Nutrient Signaling Pathways
Open this publication in new window or tab >>Studies of Budding Yeast Transcription Factors Acting Downstream of Nutrient Signaling Pathways
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Being able to respond to extracellular cues such as nutrients and growth factors is of vital importance to all living cells. Pathways have therefore evolved which can sense the extracellular status, transmit a signal through the cell and affect gene expression, which ultimately enables adaptation. Intriguingly, research has revealed that such signaling pathways responding to nutrient status are intrinsically linked to the lifespan of organisms, a phenomenon known as caloric restriction. This thesis utilizes budding yeast, Saccharomyces cerevisiae, as a model system to investigate how transcription factors affect gene expression in response to nutrient signaling pathways.

Paper I investigates the role of the three homologous transcription factors Mig1, Mig2 and Mig3 in regulating gene expression in response to glucose. This is done by transcriptional profiling with microarrays of wild type yeast, as well as mutant strains where the MIG1, MIG2 and MIG3 genes have been deleted in all possible combinations. The results reveal that Mig1 and Mig2 act together, with Mig1 having a larger effect in general while Mig2 has a role specialized for high-glucose conditions.

Using a strategy similar to that in paper I, paper II examines the roles of the two homologous transcription factors Gis1 and Rph1 in gene regulation. This study shows that Gis1 and Rph1 are both involved in nutrient signaling, acting in parallel with a large degree of redundancy. Furthermore, we find that these two transcription factors change both target genes as well as the effects on transcription when the yeast cell transitions through different growth phases.

Rph1 is a functional JmjC histone demethylase, and paper III investigates the connection between this activity and the transcriptional regulation studied in paper II. We find that rendering Rph1 catalytically inactive has little effect on its role in nutrient signaling and gene regulation, but subtly affects certain groups of genes.

Paper IV reveals that Rph1 does not affect the chronological lifespan of yeast as does its homolog Gis1. However, deleting or overexpressing RPH1 has effects on the response to rapamycin and caffeine, inhibitors of the evolutionary conserved TORC1 complex affecting lifespan in both yeast and mammals.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. 69 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 779
Keyword
Budding yeast, nutrient signaling, glucose repression, aging, caloric restriction, JmjC, histone demethylation, Mig1, Mig2, Mig3, Gis1, Rph1
National Category
Biological Sciences Genetics Microbiology
Research subject
Molecular Genetics
Identifiers
urn:nbn:se:uu:diva-173125 (URN)978-91-554-8383-8 (ISBN)
Public defence
2012-06-12, C10:301, BMC, Husargatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2012-05-21 Created: 2012-04-19 Last updated: 2012-08-01Bibliographically approved

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