THOC4 regulates energy homeostasis by stabilizing TFEB mRNA during prolonged starvation
© 2021. Published by The Company of Biologists Ltd..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:134 |
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| Enthalten in: |
Journal of cell science - 134(2021), 6 vom: 22. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Fujita, Toshiharu [VerfasserIn] |
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| Links: |
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| Themen: |
Autophagy |
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| Anmerkungen: |
Date Completed 12.07.2021 Date Revised 12.07.2021 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1242/jcs.248203 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM321488954 |
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| 500 | |a Date Revised 12.07.2021 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021. Published by The Company of Biologists Ltd. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Autophagy | |
| 650 | 4 | |a Lipid catabolism | |
| 650 | 4 | |a TFEB | |
| 650 | 4 | |a THOC4 | |
| 650 | 4 | |a mRNA stability | |
| 650 | 7 | |a Basic Helix-Loop-Helix Leucine Zipper Transcription Factors |2 NLM | |
| 650 | 7 | |a RNA, Messenger |2 NLM | |
| 700 | 1 | |a Kubo, Sayaka |e verfasserin |4 aut | |
| 700 | 1 | |a Shioda, Tatsuya |e verfasserin |4 aut | |
| 700 | 1 | |a Tokumura, Ayaka |e verfasserin |4 aut | |
| 700 | 1 | |a Minami, Satoshi |e verfasserin |4 aut | |
| 700 | 1 | |a Tsuchiya, Megumi |e verfasserin |4 aut | |
| 700 | 1 | |a Isaka, Yoshitaka |e verfasserin |4 aut | |
| 700 | 1 | |a Ogawa, Hidesato |e verfasserin |4 aut | |
| 700 | 1 | |a Hamasaki, Maho |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Li |e verfasserin |4 aut | |
| 700 | 1 | |a Yoshimori, Tamotsu |e verfasserin |4 aut | |
| 700 | 1 | |a Nakamura, Shuhei |e verfasserin |4 aut | |
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