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bioRxiv · 10.1101/2023.05.16.540835

Structural insights into human TFIIIC promoter recognition

Seifert Davila, W. H.·Girbig, M.·Hauptmann, L.·Hoffmann, T.·Eustermann, S.·Mueller, C.
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Abstract

Transcription factor IIIC (TFIIIC) recruits RNA polymerase (Pol) III to most of its target genes. Recognition of intragenic A- and B-box motifs in tRNA genes by TFIIIC modules {tau}A and {tau}B is the first critical step for tRNA synthesis but is mechanistically poorly understood. Here, we report cryo-EM structures of the human 624 kDa TFIIIC complex unbound and bound to a tRNA gene. The {tau}B module recognizes the B-box via DNA shape and sequence readout through the assembly of multiple winged-helix domains. TFIIIC220 forms an integral part of both {tau}A and {tau}B connecting the two subcomplexes via a [~]550 amino acid residue flexible linker. Our data provide a structural mechanism by which high-affinity B-box recognition anchors TFIIIC to promoter DNA and permits scanning for low-affinity A-boxes and TFIIIB for Pol III activation.

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Seifert Davila, W. H., Girbig, M., Hauptmann, L., Hoffmann, T., Eustermann, S., Mueller, C.. 2023-05-16. Structural insights into human TFIIIC promoter recognition. https://doi.org/10.1101/2023.05.16.540835

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