Structural insights into human TFIIIC promoter recognition.

Wolfram Seifert-Davila, Mathias Girbig, Luis Hauptmann, Thomas Hoffmann, Sebastian Eustermann, Christoph W Müller

Science advances 2023 Jul 07

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Transcription factor (TF) IIIC recruits RNA polymerase (Pol) III to most of its target genes. Recognition of intragenic A- and B-box motifs in transfer RNA (tRNA) genes by TFIIIC modules τA and τB is the first critical step for tRNA synthesis but is mechanistically poorly understood. Here, we report cryo-electron microscopy structures of the six-subunit human TFIIIC complex unbound and bound to a tRNA gene. The τB 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 τA and τB 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.

Citation

Wolfram Seifert-Davila, Mathias Girbig, Luis Hauptmann, Thomas Hoffmann, Sebastian Eustermann, Christoph W Müller. Structural insights into human TFIIIC promoter recognition. Science advances. 2023 Jul 07;9(27):eadh2019