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

Andrea Bernardini, Pooja Mukherjee, Elisabeth Scheer, Ivanka Kamenova, Simona Antonova, Paulina Karen Mendoza Sanchez, Gizem Yayli, Bastien Morlet, H T Marc Timmers, László Tora

Nature structural & molecular biology 2023 Aug

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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. © 2023. The Author(s).

Citation

Andrea Bernardini, Pooja Mukherjee, Elisabeth Scheer, Ivanka Kamenova, Simona Antonova, Paulina Karen Mendoza Sanchez, Gizem Yayli, Bastien Morlet, H T Marc Timmers, László Tora. Hierarchical TAF1-dependent co-translational assembly of the basal transcription factor TFIID. Nature structural & molecular biology. 2023 Aug;30(8):1141-1152