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

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. Here, the authors combine RNA-immunoprecipitation, single-molecule imaging and proteomics to chart the co-translational assembly pathway of the large general transcription factor TFIID complex from its component building blocks.

Automated summary

In this study, the authors investigate the co-translational assembly pathway of the TFIID complex by using RNA-immunoprecipitation, single-molecule imaging, and proteomics. They discover that TAF1 plays a critical role in TFIID assembly by serving as a flexible scaffold for the co-translational recruitment of preassembled submodules. These findings provide insights into the biogenesis of TFIID and potentially other large protein complexes.