WTAP Mediated N6-methyladenosine RNA Modification of ELF3 Drives Cellular Senescence by Upregulating IRF8
© The author(s)..
N6-methyladenosine (m6A), the most prevalent posttranscriptional RNA modification, involved in various diseases and cellular processes. However, the underlying mechanisms of m6A regulation in skin aging are still not fully understood. In this study, proteomics analysis revealed a significant correlation between Wilms' tumor 1-associating protein (WTAP) expression and cellular senescence. Next, upregulated WTAP was detected in aging skin tissues and senescent human dermal fibroblasts (HDFs). Functionally, overexpressed WTAP induced senescence and knockdown of WTAP rescued senescence of HDFs. Mechanistically, WTAP directly targeted ELF3 and promoted its expression in an m6A-dependent manner. Exogenous-ELF3 overexpression evidently reversed shWTAP-suppressed fibroblast senescence. Furthermore, ELF3 induced IRF8-mediated senescence-associated secretory phenotype (SASP) by binding to the (-817 to -804) site of the IRF8 promoter directly. In vivo, overexpression of WTAP evidently increased senescence cells in skin and induced skin aging. In summary, these findings revealed the critical role of WTAP-mediated m6A modification in skin aging and identified ELF3 as an important target of m6A modification in HDFs senescence, providing a new idea for delaying the aging process.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:20 |
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| Enthalten in: |
International journal of biological sciences - 20(2024), 5 vom: 22., Seite 1763-1777 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhou, Lei [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 15.03.2024 Date Revised 15.03.2024 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.7150/ijbs.90459 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM369715012 |
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| 100 | 1 | |a Zhou, Lei |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a WTAP Mediated N6-methyladenosine RNA Modification of ELF3 Drives Cellular Senescence by Upregulating IRF8 |
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| 520 | |a © The author(s). | ||
| 520 | |a N6-methyladenosine (m6A), the most prevalent posttranscriptional RNA modification, involved in various diseases and cellular processes. However, the underlying mechanisms of m6A regulation in skin aging are still not fully understood. In this study, proteomics analysis revealed a significant correlation between Wilms' tumor 1-associating protein (WTAP) expression and cellular senescence. Next, upregulated WTAP was detected in aging skin tissues and senescent human dermal fibroblasts (HDFs). Functionally, overexpressed WTAP induced senescence and knockdown of WTAP rescued senescence of HDFs. Mechanistically, WTAP directly targeted ELF3 and promoted its expression in an m6A-dependent manner. Exogenous-ELF3 overexpression evidently reversed shWTAP-suppressed fibroblast senescence. Furthermore, ELF3 induced IRF8-mediated senescence-associated secretory phenotype (SASP) by binding to the (-817 to -804) site of the IRF8 promoter directly. In vivo, overexpression of WTAP evidently increased senescence cells in skin and induced skin aging. In summary, these findings revealed the critical role of WTAP-mediated m6A modification in skin aging and identified ELF3 as an important target of m6A modification in HDFs senescence, providing a new idea for delaying the aging process | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a ELF3 | |
| 650 | 4 | |a IRF8 | |
| 650 | 4 | |a WTAP | |
| 650 | 4 | |a m6A | |
| 650 | 4 | |a senescence | |
| 650 | 7 | |a Adenosine |2 NLM | |
| 650 | 7 | |a K72T3FS567 |2 NLM | |
| 650 | 7 | |a Cell Cycle Proteins |2 NLM | |
| 650 | 7 | |a DNA-Binding Proteins |2 NLM | |
| 650 | 7 | |a ELF3 protein, human |2 NLM | |
| 650 | 7 | |a Interferon Regulatory Factors |2 NLM | |
| 650 | 7 | |a Proto-Oncogene Proteins c-ets |2 NLM | |
| 650 | 7 | |a RNA |2 NLM | |
| 650 | 7 | |a 63231-63-0 |2 NLM | |
| 650 | 7 | |a RNA Splicing Factors |2 NLM | |
| 650 | 7 | |a Transcription Factors |2 NLM | |
| 650 | 7 | |a WTAP protein, human |2 NLM | |
| 650 | 7 | |a interferon regulatory factor-8 |2 NLM | |
| 700 | 1 | |a Zhong, Yun |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Fan |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Mao, Rui |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Hongfu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yiya |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Ji |e verfasserin |4 aut | |
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| 773 | 1 | 8 | |g volume:20 |g year:2024 |g number:5 |g day:22 |g pages:1763-1777 |
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