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基础转录因子TFIID的分层TAF1依赖性共翻译组装

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

作者信息

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

机构信息

Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France.

Centre National de la Recherche Scientifique, UMR7104, Illkirch, France.

出版信息

bioRxiv. 2023 Apr 5:2023.04.05.535704. doi: 10.1101/2023.04.05.535704.

DOI:10.1101/2023.04.05.535704
PMID:37066372
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10104070/
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.

摘要

大型异源多蛋白复合物在真核细胞基因表达的每一步都发挥着关键作用。其中，由20个亚基组成的基础转录因子TFIID在基因启动子处形成RNA聚合酶II预起始复合物。在此，通过结合系统性RNA免疫沉淀（RIP）实验、单分子成像、蛋白质组学和结构功能分析，我们表明TFIID的生物发生是在共翻译过程中发生的。我们发现所有蛋白质异二聚化步骤都发生在蛋白质合成过程中。我们确定TAF1（复合物中最大的蛋白质）是TFIID组装的关键因素。TAF1作为一个灵活的支架，驱动在细胞质中预组装的TFIID亚模块的共翻译招募。总之，我们的数据提出了一个TFIID生物发生的多步骤层次模型，该模型最终以复合物在新生TAF1多肽上的共翻译组装为终点。我们设想这种组装策略可能与其他大型异源蛋白复合物共享。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c935/10104070/aa6a2877aab3/nihpp-2023.04.05.535704v1-f0007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c935/10104070/e6fecfc5d4f1/nihpp-2023.04.05.535704v1-f0011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c935/10104070/27a67b99561b/nihpp-2023.04.05.535704v1-f0012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c935/10104070/6577349f567f/nihpp-2023.04.05.535704v1-f0013.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c935/10104070/dbe45be6e055/nihpp-2023.04.05.535704v1-f0002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c935/10104070/4b080154ef4a/nihpp-2023.04.05.535704v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c935/10104070/bb596a20b5ff/nihpp-2023.04.05.535704v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c935/10104070/b768ea0ff334/nihpp-2023.04.05.535704v1-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c935/10104070/aa6a2877aab3/nihpp-2023.04.05.535704v1-f0007.jpg

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