Asr1p, a novel yeast RNA Polymerase II CTD-binding protein signals alcohol stress to the nucleus

• Applicant: Privatdozentin Dr. Susanne Bailer, Ph.D.
• Subject Area: Cell Biology
• Term: from 2005 to 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5448942

Cells sense unfavorable conditions as potentially stressful, communicate it among other things to the nucleus and respond to it by altered transcriptional activity. The baker¿s yeast S. cerevisiae serves as a simple model organism to analyse signal transduction and regulation of gene expression in response to alcohol stress. Alcohol has pleiotropic effects on the physiology of the cell. Primarily, alcohol alters the membrane structure and denatures proteins. To compensate this stressful situation that occurs during fermentation, yeast cells respond with altered transcriptional activity. We have identified a novel protein of baker¿s yeast required for vital growth in presence of alcohol and thus for repair or adaptation processes. Asr1p (Alcohol sensitive RING/PHD finger 1 protein) constitutively shuttles between cytoplasm and nucleus but accumulates in the nucleus upon alcohol stress. Asr1p responds specifically and reversibly to alcohol but not to starvation, heat, osmotic or oxidative stress. In contrast to specific transcription factors, Asr1p does not bind to promoter regions but targets the C-terminal domain (CTD) of the largest subunit Rpb1p of RNA-Polymerase II, a domain crucial for regulation and integration of transcriptional activities. Since Asr1p is the first yeast protein reported that changes its subcellular localization specifically upon alcohol stress, it provides a key to unravel alcohol induced signaling events and transcriptional regulation during alcohol stress.

• DFG Programme: Research Grants