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

Fiche publication


Date publication

juin 2023

Journal

Nature structural & molecular biology

Auteurs

Membres identifiés du Cancéropôle Est :
Dr TORA Laszlo, Mr MORLET Bastien


Tous les auteurs :
Bernardini A, Mukherjee P, Scheer E, Kamenova I, Antonova S, Mendoza Sanchez PK, Yayli G, Morlet B, Timmers HTM, Tora L

Résumé

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.

Référence

Nat Struct Mol Biol. 2023 06 29;: