Regulation der zellulären Differenzierung und Ploidie von Saccharomyces cerevisiae durch das RNA-Bindeprotein Whi3

In der Bäckerhefe Saccharomyces cerevisiae ist das RNA-Bindeprotein (RBP) Whi3 an der Regulation diverser Prozesse des Zellwachstums und der Entwicklung beteiligt. Welche Signalwege und Effektoren Whi3 für diese Kontrolle beeinflusst, ist jedoch weitestgehend unverstanden und lediglich im Rahmen der...

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Bibliographic Details
Main Author: Schladebeck, Sarah
Contributors: Mösch, Hans-Ulrich (Prof. Dr. ) (Thesis advisor)
Format: Doctoral Thesis
Language:German
Published: Philipps-Universität Marburg 2013
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In Saccharomyces cerevisiae the RNA-binding protein Whi3 is involved in the regulation of diverse processes of cell growth and development. However, the Whi3-regulated effectors and signaling pathways remain largely unknown. Concerning cell size control, Whi3 has been proposed to inhibit the G1/S-transition through cytoplasmic retention of Cdc28-Cln3, but further hints suggest that Whi3 might govern this process by additional mechanisms. This study identified several yet unknown targets of Whi3 for the control of cell cycle progression and biofilm formation including the G1 cyclins Cln1/2 as well as three biofilm regulators, the PKA subunit Tpk1, the DYRK family kinase Yak1 and the transcription factor Tec1. This study provides evidence that Whi3 regulates the production of these factors through posttranscriptional control and might exert this function by affecting translational elongation. Interestingly, here, Whi3 has been linked for the first time to control of ploidy stability, because whi3-deficient strains exhibit a significant increase-in-ploidy phenotype that depends on environmental conditions. The data obtained in this study suggests that Whi3 might guarantee genome integrity by controlling the expression of several genes involved in sister chromatid cohesion and the dynactin complex component NIP100 thereby ensuring faithful chromosome segregation. Finally, this study provides new insights into the Whi3-mediated stress response. The RBP is required for the stress-induced expression of the surface flocculin FLO11 as well as for the general stress response and probably targets Yak1- and the stress transcription factors Msn2/4. Moreover, the deletion of WHI3 seems to trigger a cellular transcriptional stress response by Yak1-independent mechanisms, which is reverted by whole genome duplication. In summary, this study suggests that the RBP Whi3 is a central regulator of cell growth and development, which is able to ensure appropriate signaling capacity of regulatory networks through sufficient supply of diverse key regulators.