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

Bernardini, A.; Mukherjee, P.; Scheer, E.; Kamenova, I.; Antonova, S.; Sanchez, P. K. M.; Yayli, G.; Morlet, B.; Timmers, H. T. M.; Tora, L.

doi:10.1101/2023.04.05.535704

bioRxiv · 10.1101/2023.04.05.535704

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

Bernardini, A.·Mukherjee, P.·Scheer, E.·Kamenova, I.·Antonova, S.·Sanchez, P. K. M.·Yayli, G.·Morlet, B.·Timmers, H. T. M.·Tora, L.

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Abstract

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 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 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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Bernardini, A., Mukherjee, P., Scheer, E., Kamenova, I., Antonova, S., Sanchez, P. K. M., Yayli, G., Morlet, B., Timmers, H. T. M., Tora, L.. 2023-04-05. Hierarchical TAF1-dependent co-translational assembly of the basal transcription factor TFIID. https://doi.org/10.1101/2023.04.05.535704

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