Mechanism of RNA polymerase I selection by transcription factor UAF.

Baudin, Florence; Murciano, Brice; Fung, Herman K H; Fromm, Simon A; Mattei, Simone; Mahamid, Julia; Müller, Christoph W · Sci Adv · 2022

basic_science · Level V

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Abstract

Preribosomal 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 at the 35<i>S</i> ribosomal RNA gene. To visualize the molecular intermediates toward PIC formation, we determined the structure of UAF in complex with native promoter DNA and transcription factor TATA-box-binding protein (TBP). We found that UAF recognizes DNA using a hexameric histone-like scaffold with markedly different interactions compared with the nucleosome and the histone-fold-rich transcription factor IID (TFIID). In parallel, UAF positions TBP for Core Factor binding, which leads to Pol I recruitment, while sequestering it from DNA and Pol II/III-specific transcription factors. Our work thus reveals the structural basis of RNA Pol selection by a transcription factor.

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