The nuclear transcription factor, TAF7, is a cytoplasmic regulator of protein synthesis

Dan Cheng; Kevin Semmens; Elizabeth McManus; Qingrong Chen; Daoud Meerzaman; Xiantao Wang; Markus Hafner; Brian A Lewis; Hidehisa Takahashi; Ballachanda N Devaiah; Anne Gegonne; Dinah S Singer

doi:10.1126/sciadv.abi5751

The nuclear transcription factor, TAF7, is a cytoplasmic regulator of protein synthesis

Sci Adv. 2021 Dec 10;7(50):eabi5751. doi: 10.1126/sciadv.abi5751. Epub 2021 Dec 10.

Authors

Affiliations

¹ Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
² School of Medicine, University of Utah, Salt Lake City, UT 84132, USA.
³ Center for Biomedical Informatics and Information Technology, National Cancer Institute, NIH, Rockville, MD 20850, USA.
⁴ Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD 20892, USA.
⁵ Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
⁶ Department of Molecular Biology, Yokohama City University Graduate School of Medical Science, Fukuura 3-9, Kanazawa-ku, Yokohama, Kanagawa 216-0004, Japan.

Abstract

The TFIID component, TAF7, has been extensively characterized as essential for transcription and is critical for cell proliferation and differentiation. Here, we report that TAF7 is a previously unknown RNA chaperone that contributes to the regulation of protein synthesis. Mechanistically, TAF7 binds RNAs in the nucleus and delivers them to cytoplasmic polysomes. A broad spectrum of target RNA species, including the HIV-1 transactivation response element, binds TAF7 through consensus CUG motifs within the 3′ untranslated region. Export to the cytoplasm depends on a TAF7 nuclear export signal and occurs by an exportin 1–dependent pathway. Notably, disrupting either TAF7’s RNA binding or its export from the nucleus results in retention of target messenger RNAs in the nucleus and reduced levels of the protein products of TAF7-target RNAs. Thus, TAF7, an essential transcription factor, plays a key role in the regulation of RNA translation, thereby potentially connecting these processes.