フジタ　トシハル   Toshiharu Fujita   藤田　敏治    所属   川崎医科大学  医学部 基礎医学　分子遺伝医学    職種   助教
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	THOC4 regulates energy homeostasis by stabilizing TFEB mRNA during prolonged starvation.
掲載誌名	正式名：Journal of cell science 略　 称：J Cell Sci ISSNコード：14779137/00219533
掲載区分	国外
巻・号・頁	134(6)
著者・共著者	Toshiharu Fujita, Sayaka Kubo, Tatsuya Shioda, Ayaka Tokumura, Satoshi Minami, Megumi Tsuchiya, Yoshitaka Isaka, Hidesato Ogawa, Maho Hamasaki, Li Yu, Tamotsu Yoshimori, Shuhei Nakamura
発行年月	2021/03
概要	TFEB, a basic helix-loop-helix transcription factor, is a master regulator of autophagy, lysosome biogenesis and lipid catabolism. Compared to posttranslational regulation of TFEB, the regulation of TFEB mRNA stability remains relatively uncharacterized. In this study, we identified the mRNA-binding protein THOC4 as a novel regulator of TFEB. In mammalian cells, siRNA-mediated knockdown of THOC4 decreased the level of TFEB protein to a greater extent than other bHLH transcription factors. THOC4 bound to TFEB mRNA and stabilized it after transcription by maintaining poly(A) tail length. We further found that this mode of regulation was conserved in Caenorhabditiselegans and was essential for TFEB-mediated lipid breakdown, which becomes over-represented during prolonged starvation. Taken together, our findings reveal the presence of an additional layer of TFEB regulation by THOC4 and provide novel insights into the function of TFEB in mediating autophagy and lipid metabolism.
DOI	10.1242/jcs.248203
PMID	33589500