Zomerdijk, Joost

Molecular mechanisms and control in transcription by RNA polymerase I

Appropriately coordinated expression of genes is essential for normal cell growth, development and differentiation in all organisms. The control of expression of many genes in eukaryotes occurs at the level of transcription. The central objective in our laboratory is to achieve an understanding of the molecular mechanisms involved in transcription of the ribosomal RNA genes, mediated by RNA polymerase I, and the cellular control of this process (1,2). rRNA synthesis drives ribosome biogenesis and, therefore, is associated intricately with cell growth and proliferation. Deregulation of this process can lead to cell death, hyperproliferation or hypertrophy and has been linked to specific cancers and heart disease.

Our research is directed towards determination of:

• the role of the essential promoter selective TBP-TAF complex SL1 in coordinating the formation of transcription pre-initiation complexes (3,4);
• the molecular mechanism of activation by UBF of promoter escape by Pol I (5,6)
• the dynamics of the Pol I proteome (7)
• the link between cell growth and proliferation and Pol I transcription (7,8)
• the factors involved in promoting transcription elongation and re-initiation
• the roles of novel growth-regulated and Pol I-associated factors in human cells (7,9,10)