GRK 2243 "Understanding Ubiquitylation: From Molecular Mechanisms to Disease"

Project C5

Role of RNA Polymerase II ubiquitylation in transcription

Elmar Wolf

The function of RNA Polymerase II (Pol2) is essential for eukaryotes as it transcribes all cellular mRNA. Consequently, deregulated transcription is linked to various human diseases. A prime example are malignant tumors, as continuously proliferating cancer cells depend on altered gene expression profiles and elevated transcription rates [1].

The process of transcription is composed of several consecutive functional steps called the transcriptional cycle. Regulation of transcription and the correct succession of Pol2 in the transcriptional cycle is critically determined by post-translational modifications. While phosphorylation is certainly the best understood post-transcriptional modification of Pol2, ubiquitylation also plays a fundamental role in transcriptional control and was initially observed as a “last resort” mechanism upon DNA damage in yeast. However, ubiquitylation of Pol2 is much less investigated in the mammalian system. Importantly, it is completely unclear if and how ubiquitylation controls the transcriptional cycle in unstressed cells. Therefore, we propose to study the impact and mechanistical details of ubiquitylation of human Pol2 on normal transcription.