YTHDF1-CLOCK axis contributes to pathogenesis of allergic airway inflammation through LLPS
Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved..
N6-methyladenosine (m6A) modification has been implicated in many cell processes and diseases. YTHDF1, a translation-facilitating m6A reader, has not been previously shown to be related to allergic airway inflammation. Here, we report that YTHDF1 is highly expressed in allergic airway epithelial cells and asthmatic patients and that it influences proinflammatory responses. CLOCK, a subunit of the circadian clock pathway, is the direct target of YTHDF1. YTHDF1 augments CLOCK translation in an m6A-dependent manner. Allergens enhance the liquid-liquid phase separation (LLPS) of YTHDF1 and drive the formation of a complex comprising dimeric YTHDF1 and CLOCK mRNA, which is distributed to stress granules. Moreover, YTHDF1 strongly activates NLRP3 inflammasome production and interleukin-1β secretion leading to airway inflammatory responses, but these phenotypes are abolished by deleting CLOCK. These findings demonstrate that YTHDF1 is an important regulator of asthmatic airway inflammation, suggesting a potential therapeutic target for allergic airway inflammation.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:43 |
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| Enthalten in: |
Cell reports - 43(2024), 3 vom: 26. März, Seite 113947 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Jing [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 01.04.2024 Date Revised 03.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.celrep.2024.113947 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369818970 |
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| 245 | 1 | 0 | |a YTHDF1-CLOCK axis contributes to pathogenesis of allergic airway inflammation through LLPS |
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| 520 | |a Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a N6-methyladenosine (m6A) modification has been implicated in many cell processes and diseases. YTHDF1, a translation-facilitating m6A reader, has not been previously shown to be related to allergic airway inflammation. Here, we report that YTHDF1 is highly expressed in allergic airway epithelial cells and asthmatic patients and that it influences proinflammatory responses. CLOCK, a subunit of the circadian clock pathway, is the direct target of YTHDF1. YTHDF1 augments CLOCK translation in an m6A-dependent manner. Allergens enhance the liquid-liquid phase separation (LLPS) of YTHDF1 and drive the formation of a complex comprising dimeric YTHDF1 and CLOCK mRNA, which is distributed to stress granules. Moreover, YTHDF1 strongly activates NLRP3 inflammasome production and interleukin-1β secretion leading to airway inflammatory responses, but these phenotypes are abolished by deleting CLOCK. These findings demonstrate that YTHDF1 is an important regulator of asthmatic airway inflammation, suggesting a potential therapeutic target for allergic airway inflammation | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a CP: Immunology | |
| 650 | 4 | |a CP: Molecular biology | |
| 650 | 4 | |a N6-methyladenosine | |
| 650 | 4 | |a YTHDF1 | |
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| 700 | 1 | |a Zhang, Meng |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Yujiao |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Qun |e verfasserin |4 aut | |
| 700 | 1 | |a Su, Wen |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Min |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Jinhong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Min |e verfasserin |4 aut | |
| 700 | 1 | |a Shuai, Jianwei |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Lv, Jiajia |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Min |e verfasserin |4 aut | |
| 700 | 1 | |a Xia, Zhenwei |e verfasserin |4 aut | |
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