YTHDF1-CLOCK axis contributes to pathogenesis of allergic airway inflammation through LLPS
Summary: 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 epith...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-03-01
|
| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724002754 |
| _version_ | 1797260347991654400 |
|---|---|
| author | Jing Wang Yao Zhou Meng Zhang Yujiao Wu Qun Wu Wen Su Min Xu Jinhong Wu Min Zhang Jianwei Shuai Wei Tang Jiajia Lv Min Wu Zhenwei Xia |
| author_facet | Jing Wang Yao Zhou Meng Zhang Yujiao Wu Qun Wu Wen Su Min Xu Jinhong Wu Min Zhang Jianwei Shuai Wei Tang Jiajia Lv Min Wu Zhenwei Xia |
| author_sort | Jing Wang |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-04-24T23:23:53Z |
| format | Article |
| id | doaj.art-7b4f93fd66ef451988be73ab197f0dd1 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-24T23:23:53Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-7b4f93fd66ef451988be73ab197f0dd12024-03-16T05:08:18ZengElsevierCell Reports2211-12472024-03-01433113947YTHDF1-CLOCK axis contributes to pathogenesis of allergic airway inflammation through LLPSJing Wang0Yao Zhou1Meng Zhang2Yujiao Wu3Qun Wu4Wen Su5Min Xu6Jinhong Wu7Min Zhang8Jianwei Shuai9Wei Tang10Jiajia Lv11Min Wu12Zhenwei Xia13Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Surgery, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Surgery, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Surgery, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Surgery, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaJoint Research Centre on Medicine, The Affiliated Xiangshan Hospital of Wenzhou Medical University, Ningbo, China; Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, ChinaDepartment of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Corresponding AuthorDepartment of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Corresponding AuthorJoint Research Centre on Medicine, The Affiliated Xiangshan Hospital of Wenzhou Medical University, Ningbo, China; Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, China; Corresponding authorDepartment of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124724002754CP: Molecular biologyCP: Immunology |
| spellingShingle | Jing Wang Yao Zhou Meng Zhang Yujiao Wu Qun Wu Wen Su Min Xu Jinhong Wu Min Zhang Jianwei Shuai Wei Tang Jiajia Lv Min Wu Zhenwei Xia YTHDF1-CLOCK axis contributes to pathogenesis of allergic airway inflammation through LLPS Cell Reports CP: Molecular biology CP: Immunology |
| title | YTHDF1-CLOCK axis contributes to pathogenesis of allergic airway inflammation through LLPS |
| title_full | YTHDF1-CLOCK axis contributes to pathogenesis of allergic airway inflammation through LLPS |
| title_fullStr | YTHDF1-CLOCK axis contributes to pathogenesis of allergic airway inflammation through LLPS |
| title_full_unstemmed | YTHDF1-CLOCK axis contributes to pathogenesis of allergic airway inflammation through LLPS |
| title_short | YTHDF1-CLOCK axis contributes to pathogenesis of allergic airway inflammation through LLPS |
| title_sort | ythdf1 clock axis contributes to pathogenesis of allergic airway inflammation through llps |
| topic | CP: Molecular biology CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724002754 |
| work_keys_str_mv | AT jingwang ythdf1clockaxiscontributestopathogenesisofallergicairwayinflammationthroughllps AT yaozhou ythdf1clockaxiscontributestopathogenesisofallergicairwayinflammationthroughllps AT mengzhang ythdf1clockaxiscontributestopathogenesisofallergicairwayinflammationthroughllps AT yujiaowu ythdf1clockaxiscontributestopathogenesisofallergicairwayinflammationthroughllps AT qunwu ythdf1clockaxiscontributestopathogenesisofallergicairwayinflammationthroughllps AT wensu ythdf1clockaxiscontributestopathogenesisofallergicairwayinflammationthroughllps AT minxu ythdf1clockaxiscontributestopathogenesisofallergicairwayinflammationthroughllps AT jinhongwu ythdf1clockaxiscontributestopathogenesisofallergicairwayinflammationthroughllps AT minzhang ythdf1clockaxiscontributestopathogenesisofallergicairwayinflammationthroughllps AT jianweishuai ythdf1clockaxiscontributestopathogenesisofallergicairwayinflammationthroughllps AT weitang ythdf1clockaxiscontributestopathogenesisofallergicairwayinflammationthroughllps AT jiajialv ythdf1clockaxiscontributestopathogenesisofallergicairwayinflammationthroughllps AT minwu ythdf1clockaxiscontributestopathogenesisofallergicairwayinflammationthroughllps AT zhenweixia ythdf1clockaxiscontributestopathogenesisofallergicairwayinflammationthroughllps |