Architecture of TAF11/TAF13/TBP complex suggests novel regulation properties of general transcription factor TFIID
- University of Bristol, United Kingdom
- University of Cambridge, United Kingdom
- Institut de Génétique et de Biologie Moléculaire et Cellulaire, IGBMC, France
- European Molecular Biology Laboratory, Germany
- University of Edinburgh, United Kingdom
- Physical and Theoretical Chemistry Laboratory, United Kingdom
- European Molecular Biology Laboratory, France
- Institut de Biologie Structurale, France
- Academy of Sciences of the Czech Republic, Czech Republic
Abstract
General transcription factor TFIID is a key component of RNA polymerase II transcription initiation. Human TFIID is a megadalton-sized complex comprising TATA-binding protein (TBP) and 13 TBP-associated factors (TAFs). TBP binds to core promoter DNA, recognizing the TATA-box. We identified a ternary complex formed by TBP and the histone fold (HF) domain-containing TFIID subunits TAF11 and TAF13. We demonstrate that TAF11/TAF13 competes for TBP binding with TATA-box DNA, and also with the N-terminal domain of TAF1 previously implicated in TATA-box mimicry. In an integrative approach combining crystal coordinates, biochemical analyses and data from cross-linking mass-spectrometry (CLMS), we determine the architecture of the TAF11/TAF13/TBP complex, revealing TAF11/TAF13 interaction with the DNA binding surface of TBP. We identify a highly conserved C-terminal TBP-interaction domain (CTID) in TAF13 which is essential for supporting cell growth. Our results thus have implications for cellular TFIID assembly and suggest a novel regulatory state for TFIID function.
Data availability
Article and author information
Author details
Funding
Wellcome
- Imre Berger
H2020 European Research Council (ERC-2013-340551)
- Làszlò Tora
Research Councils UK
- Imre Berger
Agence Nationale de la Recherche (ANR-13-BSV8-0021-03)
- Imre Berger
Baden-Württemberg Stiftung
- Imre Berger
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Cynthia Wolberger, Johns Hopkins University, United States
Publication history
- Received: July 13, 2017
- Accepted: November 3, 2017
- Accepted Manuscript published: November 7, 2017 (version 1)
- Version of Record published: November 16, 2017 (version 2)
Copyright
© 2017, Gupta et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 3,138
- Page views
-
- 516
- Downloads
-
- 23
- Citations
Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Architecture of TAF11/TAF13/TBP complex suggests novel regulation properties of general transcription factor TFIID
eLife 6:e30395.
https://doi.org/10.7554/eLife.30395
Further reading
-
- Biochemistry and Chemical Biology
- Chromosomes and Gene Expression
N6-methyladenosine (m6A) RNA modification impacts mRNA fate primarily via reader proteins, which dictate processes in development, stress, and disease. Yet little is known about m6A function in Saccharomyces cerevisiae, which occurs solely during early meiosis. Here we perform a multifaceted analysis of the m6A reader protein Pho92/Mrb1. Cross-linking immunoprecipitation analysis reveals that Pho92 associates with the 3’end of meiotic mRNAs in both an m6A-dependent and independent manner. Within cells, Pho92 transitions from the nucleus to the cytoplasm, and associates with translating ribosomes. In the nucleus Pho92 associates with target loci through its interaction with transcriptional elongator Paf1C. Functionally, we show that Pho92 promotes and links protein synthesis to mRNA decay. As such, the Pho92-mediated m6A-mRNA decay is contingent on active translation and the CCR4-NOT complex. We propose that the m6A reader Pho92 is loaded co-transcriptionally to facilitate protein synthesis and subsequent decay of m6A modified transcripts, and thereby promotes meiosis.
-
- Biochemistry and Chemical Biology
- Cancer Biology
The tumor suppressor gene PTEN is the second most commonly deleted gene in cancer. Such deletions often include portions of the chromosome 10q23 locus beyond the bounds of PTEN itself, which frequently disrupts adjacent genes. Coincidental loss of PTEN-adjacent genes might impose vulnerabilities that could either affect patient outcome basally or be exploited therapeutically. Here we describe how the loss of ATAD1, which is adjacent to and frequently co-deleted with PTEN, predisposes cancer cells to apoptosis triggered by proteasome dysfunction and correlates with improved survival in cancer patients. ATAD1 directly and specifically extracts the pro-apoptotic protein BIM from mitochondria to inactivate it. Cultured cells and mouse xenografts lacking ATAD1 are hypersensitive to clinically used proteasome inhibitors, which activate BIM and trigger apoptosis. This work furthers our understanding of mitochondrial protein homeostasis and could lead to new therapeutic options for the hundreds of thousands of cancer patients who have tumors with chromosome 10q23 deletion.
