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bioRxiv · 10.1101/2022.02.10.479882

Mechanism of RNA Polymerase I selection by transcription factor UAF

Baudin, F.·Murciano, B.·Fung, H. K.·Fromm, S. A.·Mattei, S.·Mahamid, J.·Müller, C. W.
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Abstract

Pre-ribosomal RNA is selectively transcribed by RNA Polymerase (Pol) I in eukaryotes. The yeast transcription factor Upstream Activating Factor (UAF) represses Pol II transcription and mediates Pol I preinitiation complex (PIC) formation during the early stages of transcription initiation at the 35S ribosomal RNA gene. To unravel the DNA recognition and Pol I selection mechanisms of UAF, we determined the structure of UAF bound to native promoter DNA and transcription factor TBP. We found that UAF recognizes DNA using a hexameric histone-like scaffold with markedly different interactions than the nucleosome and the histone-fold-rich TFIID. UAF strategically sequesters TBP from DNA and Pol II/III-specific factors, and positions it for Core Factor binding, supporting Pol I recruitment. Our findings therefore reveal the molecular basis of Pol I selection for ribosome biogenesis. As well, they reveal an unexpected potential within the histone fold as a motif for specific protein-DNA interactions inside the cell.

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Baudin, F., Murciano, B., Fung, H. K., Fromm, S. A., Mattei, S., Mahamid, J., Müller, C. W.. 2022-02-10. Mechanism of RNA Polymerase I selection by transcription factor UAF. https://doi.org/10.1101/2022.02.10.479882

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