title: Architecture of TFIIIC and its role in RNA polymerase III pre-initiation complex assembly.
abstract: In eukaryotes, RNA Polymerase III (Pol III) is specifically responsible for transcribing genes encoding tRNAs and other short non-coding RNAs. The recruitment of Pol III to tRNA-encoding genes requires the transcription factors (TF) IIIB and IIIC. TFIIIC has been described as a conserved, multi-subunit protein complex composed of two subcomplexes, called τA and τB. How these two subcomplexes are linked and how their interaction affects the formation of the Pol III pre-initiation complex (PIC) is poorly understood. Here we use chemical crosslinking mass spectrometry and determine the molecular architecture of TFIIIC. We further report the crystal structure of the essential TPR array from τA subunit τ131 and characterize its interaction with a central region of τB subunit τ138. The identified τ131-τ138 interacting region is essential in vivo and overlaps with TFIIIB-binding sites, revealing a crucial interaction platform for the regulation of tRNA transcription initiation.
authors.affiliation: European Molecular Biology Laboratory (EMBL), Structural and Computational Biology Unit, Meyerhofstrasse 1, Heidelberg 69117, Germany.
authors.forename: Gary
authors.initials: G
authors.lastname: Male
authors.affiliation: European Molecular Biology Laboratory (EMBL), Structural and Computational Biology Unit, Meyerhofstrasse 1, Heidelberg 69117, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: von Appen
authors.affiliation: European Molecular Biology Laboratory (EMBL), Structural and Computational Biology Unit, Meyerhofstrasse 1, Heidelberg 69117, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Glatt
authors.affiliation: European Molecular Biology Laboratory (EMBL), Structural and Computational Biology Unit, Meyerhofstrasse 1, Heidelberg 69117, Germany.
authors.forename: Nicholas M I
authors.initials: NM
authors.lastname: Taylor
authors.affiliation: European Molecular Biology Laboratory (EMBL), Structural and Computational Biology Unit, Meyerhofstrasse 1, Heidelberg 69117, Germany.
authors.forename: Michele
authors.initials: M
authors.lastname: Cristovao
authors.affiliation: European Molecular Biology Laboratory (EMBL), Structural and Computational Biology Unit, Meyerhofstrasse 1, Heidelberg 69117, Germany.
authors.forename: Helga
authors.initials: H
authors.lastname: Groetsch
authors.affiliation: European Molecular Biology Laboratory (EMBL), Structural and Computational Biology Unit, Meyerhofstrasse 1, Heidelberg 69117, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Beck
authors.affiliation: European Molecular Biology Laboratory (EMBL), Structural and Computational Biology Unit, Meyerhofstrasse 1, Heidelberg 69117, Germany.
authors.forename: Christoph W
authors.initials: CW
authors.lastname: Müller
mesh_terms: D018360:Crystallography, X-Ray; D012320:RNA Polymerase III / Q000737:chemistry / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D019474:Transcription Factors, TFIII / Q000737:chemistry / Q000378:metabolism*; D000098832:Transcription Factor TFIIIC
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D019474:Transcription Factors, TFIII; D000098832:Transcription Factor TFIIIC; D012320:RNA Polymerase III