PreprintCited by 23Genomics and Chromatin DynamicsRNA and protein synthesis mechanismsProtein Structure and Dynamics

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Structural insights into human TFIIIC promoter recognition

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Seifert-Davila, Wolfram, Girbig, Mathias, Hauptmann, Luis, Hoffmann, Thomas, Eustermann, Sebastian, Müller, Christoph W.·2023·Science Advances

Preprint — published as 10.1126/sciadv.adh2019

Abstract

SUMMARY: 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 τA and τB 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 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.

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Metadata

Authors
Seifert-Davila, W., Girbig, M., Hauptmann, L., Hoffmann, T., Eustermann, S., & Müller, C. W.
Affiliations
European Molecular Biology Laboratory (DE)
Corresponding author
Müller, Christoph W.
Venue
Science Advances
Publisher
openRxiv
Published
2023-05-16
Volume
9
Issue
27
Pages
eadh2019-eadh2019
ISSN
2375-2548 (ISSN-L)
OpenAlex
W4383499578
Cited by
23
References
1
Citations by year
2026: 5 · 2025: 10 · 2024: 6 · 2023: 2
FWCI
2.05
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Science Advances (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Keywords
TFIIIC, RNA polymerase III, tRNA gene transcription, promoter identification, B-box, A-box, winged-helix domain, DNA shape, flexible linkers, cryo-EM structure, TFIIIB, tRNA synthetase
MeSH terms
Transcription Factor TFIIIC, DNA, Humans, RNA, Transfer, Transcription, Genetic, Transcription Factors, TFIII, Cryoelectron Microscopy

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