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Role of the Mammalian RNA Polymerase II C-Terminal Domain (CTD) Nonconsensus Repeats in CTD Stability and Cell Proliferation

GSF-Research Centre for Environment and Health, Institute for Clinical Molecular Biology and Tumour Genetics, Marchioninistr. 25, D-81377 Munich, Germany

Received 18 April 2005/ Returned for modification 6 June 2005/ Accepted 14 June 2005

The C-terminal domain (CTD) of mammalian RNA polymerase II (Pol II) consists of 52 repeats of the consensus heptapeptide YSPTSPS and links transcription to the processing of pre-mRNA. The length of the CTD and the number of repeats diverging from the consensus sequence have increased through evolution, but their functional importance remains unknown. Here, we show that the deletion of repeats 1 to 3 or 52 leads to cleavage and degradation of the CTD from Pol II in vivo. Including these repeats, however, allowed the construction of stable, synthetic CTDs. To our surprise, polymerases consisting of just consensus repeats could support normal growth and viability of cells. We conclude that all other nonconsensus CTD repeats are dispensable for the transcription and pre-mRNA processing of genes essential for proliferation.

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