Regulation of Transcription

transcriptionThe transcription cycle is regulated by Cyclin-dependent kinases that phosphorylate the RNA polymerase II and general transcription factors. We analyze how in eukaryotic cells the transition from transcription initiation to productive elongation is mediated. 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. Two other cyclin-dependent kinases, Cdk12 and Cdk13, contribute to pre-mRNA processing and transcriptional splicing. We aim at analyzing the molecular and structural mechanisms that determine the activity and regulation of transcription-controlling kinases. The malfunction of transcriptional elongation leads to a variety of diseases as several forms of cancer, leukaemia, HIV infection and myocardial hypertrophy.