Regulation of Transcription

transcriptionThe transcription cycle is regulated by Cyclin-dependent kinases that phosphorylate the RNA polymerase II and general transcription factors. We analyse how the transition from transcription initiation to productive elongation, polyadenylation and termination is mediated in eukaryotic cells. After transcription initiation, the RNA polymerase II (RNAPII) pauses approximately 50-150 nucleotides downstream of the transcription start site. Release from this block requires the positive transcription elongation factor P-TEFb, which is a heterodimer composed of the cyclin-dependent kinase Cdk9 and the regulatory subunit Cyclin T. Cdk9 mediates the transition from transcription initiation to productive elongation of pre-mRNA transcripts by phosphorylation of the C-terminal domain (CTD) of RNAPII. Other cyclin-dependent kinases, Cdk7, CDK8, Cdk11, Cdk12 and Cdk13, contribute to transcriptional initiation, pre-mRNA processing and splicing regulation. We aim at analyzing the molecular and structural mechanisms that determine the activity and regulation of the transcription cycle controlling kinases. The malfunction of gene expression at a transcriptional level leads to a variety of diseases as multiple forms of cancer, leukaemia, HIV infection, and myocardial hypertrophy.