Hierarchical TAF1-dependent co-translational assembly of the basal transcription factor TFIID

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作者
Andrea Bernardini
Pooja Mukherjee
Elisabeth Scheer
Ivanka Kamenova
Simona Antonova
Paulina Karen Mendoza Sanchez
Gizem Yayli
Bastien Morlet
H.T. Marc Timmers
László Tora
机构
[1] Institut de Génétique et de Biologie Moléculaire et Cellulaire,
[2] Centre National de la Recherche Scientifique,undefined
[3] Institut National de la Santé et de la Recherche Médicale,undefined
[4] Université de Strasbourg,undefined
[5] German Cancer Consortium (DKTK) partner site Freiburg,undefined
[6] German Cancer Research Center (DKFZ) and Department of Urology,undefined
[7] Medical Center-University of Freiburg,undefined
[8] Innovative Genomics Institute,undefined
[9] University of California,undefined
[10] Nature Protocols,undefined
[11] The Netherlands Cancer Institute,undefined
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摘要
Large heteromeric multiprotein complexes play pivotal roles at every step of gene expression in eukaryotic cells. Among them, the 20-subunit basal transcription factor TFIID nucleates the RNA polymerase II preinitiation complex at gene promoters. Here, by combining systematic RNA-immunoprecipitation (RIP) experiments, single-molecule imaging, proteomics and structure–function analyses, we show that human TFIID biogenesis occurs co-translationally. We discovered that all protein heterodimerization steps happen during protein synthesis. We identify TAF1—the largest protein in the complex—as a critical factor for TFIID assembly. TAF1 acts as a flexible scaffold that drives the co-translational recruitment of TFIID submodules preassembled in the cytoplasm. Altogether, our data suggest a multistep hierarchical model for TFIID biogenesis that culminates with the co-translational assembly of the complex onto the nascent TAF1 polypeptide. We envision that this assembly strategy could be shared with other large heteromeric protein complexes.
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页码:1141 / 1152
页数:11
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