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

Andrea Bernardini (1) , Pooja Mukherjee (1) , Elisabeth Scheer (1) , Ivanka Kamenova (1) , Simona Antonova (2) , Paulina Karen Mendoza Sanchez (3) , Gizem Yayli (1) , Bastien Morlet (1) , H.T. Marc Timmers (3) , László Tora (1)

1 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire
2 NKI - Netherlands Cancer Institute
3 Uniklinik - Universitäts Klinikum Freiburg = University Medical Center Freiburg

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.

Domaines: Génomique, Transcriptomique et Protéomique [q-bio.GN]; Biologie structurale [q-bio.BM]

Andrea Bernardini, Pooja Mukherjee, Elisabeth Scheer, Ivanka Kamenova, Simona Antonova, et al.. Hierarchical TAF1-dependent co-translational assembly of the basal transcription factor TFIID. Nature Structural and Molecular Biology, 2023, 30 (8), pp.1141-1152. ⟨10.1038/s41594-023-01026-3⟩. ⟨hal-04173334⟩