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Structural insights into human TFIIIC promoter recognition
Open accessPreprint — 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.
- ORCID
- Venue
- Science Advances
- Publisher
- openRxiv
- Published
- 2023-05-16
- Volume
- 9
- Issue
- 27
- Pages
- eadh2019-eadh2019
- ISSN
- 2375-2548 (ISSN-L)
- PMC
- PMC11811891
- 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
- gold
- doi.org
- 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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