"Gene transcription is a highly regulated process that allows cells to adapt during different stages of development and to changes in their environmental conditions. Specifically, RNA polymerase (Pol) III is responsible for the transcription of small, untranslated genes involved in fundamental cellular process such as mRNA processing (U6 snRNA) and translation (tRNAs). Recruitment of Pol III to its transcription start site requires the general transcription factor IIIB (TFIIIB), in mammals a known target of regulation by oncogenes and tumour suppressors. TFIIIB comprises three subunits, (TBP, Brf1 and Bdp1, Mr = 162 kDa) and, despite its crucial role in Pol III transcription initiation and its involvement in cancer cell proliferation, only limited structural information is available for this factor.
The project aims to reconstitute and to structurally describe the TFIIIB complex using biochemical and structural biology approaches and to characterize interactions between TFIIIB and Pol III using a combination of X-ray crystallography and single-particle electron microscopy. Description of the architecture of individual TFIIIB subunits, the entire TFIIIB complex, or a TFIIIB/Pol III complex, will contribute to improve our understanding of Pol III recruitment and Pol III transcription initiation. Furthermore, it will provide a structural framework to further elucidate the role of TFIIIB in Pol III misregulation and cancerogenesis."
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