METTL3-Mediated m6A RNA Modification Regulates Corneal Injury Repair

Limbal stem cells are essential for continuous corneal regeneration and injury repair. METTL3-catalyzed N6-methyladenosine (m6A) mRNA modifications are involved in many biological processes and play a specific role in stem cell regeneration, while the role of m6A modifications in corneal injury repa...

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Main Authors: Yarong Dai, Maosheng Cheng, Siyan Zhang, Rongsong Ling, Jieqi Wen, Yifan Cheng, Boxuan Huang, Jinrong Li, Caifeng Dai, Shiqing Mao, Shuibin Lin, Huangxuan Shen, Yizhou Jiang
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2021/5512153
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author Yarong Dai
Maosheng Cheng
Siyan Zhang
Rongsong Ling
Jieqi Wen
Yifan Cheng
Boxuan Huang
Jinrong Li
Caifeng Dai
Shiqing Mao
Shuibin Lin
Huangxuan Shen
Yizhou Jiang
author_facet Yarong Dai
Maosheng Cheng
Siyan Zhang
Rongsong Ling
Jieqi Wen
Yifan Cheng
Boxuan Huang
Jinrong Li
Caifeng Dai
Shiqing Mao
Shuibin Lin
Huangxuan Shen
Yizhou Jiang
author_sort Yarong Dai
collection DOAJ
description Limbal stem cells are essential for continuous corneal regeneration and injury repair. METTL3-catalyzed N6-methyladenosine (m6A) mRNA modifications are involved in many biological processes and play a specific role in stem cell regeneration, while the role of m6A modifications in corneal injury repair remains unknown. In this study, we generated a limbal stem cell-specific METTL3 knockout mouse model and studied the role of m6A in repairing corneal injury caused by alkali burn. The results showed that METTL3 knockout in the limbal stem cells promotes the in vivo cell proliferation and migration, leading to the fast repair of corneal injury. In addition, m6A modification profiling identified stem cell regulatory factors AHNAK and DDIT4 as m6A targets. Our study reveals the essential functions of m6A RNA modification in regulating injury repair and provides novel insights for clinical therapy of corneal diseases.
format Article
id doaj-art-67fb4ff9e993473cb06ce8a1f0056837
institution Kabale University
issn 1687-966X
1687-9678
language English
publishDate 2021-01-01
publisher Wiley
record_format Article
series Stem Cells International
spelling doaj-art-67fb4ff9e993473cb06ce8a1f00568372025-08-20T03:33:54ZengWileyStem Cells International1687-966X1687-96782021-01-01202110.1155/2021/55121535512153METTL3-Mediated m6A RNA Modification Regulates Corneal Injury RepairYarong Dai0Maosheng Cheng1Siyan Zhang2Rongsong Ling3Jieqi Wen4Yifan Cheng5Boxuan Huang6Jinrong Li7Caifeng Dai8Shiqing Mao9Shuibin Lin10Huangxuan Shen11Yizhou Jiang12Institute for Advanced Study, Shenzhen University, 518067, ChinaAnhui Medical University, 230032, ChinaInstitute for Advanced Study, Shenzhen University, 518067, ChinaInstitute for Advanced Study, Shenzhen University, 518067, ChinaInstitute for Advanced Study, Shenzhen University, 518067, ChinaInstitute for Advanced Study, Shenzhen University, 518067, ChinaInstitute for Advanced Study, Shenzhen University, 518067, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 510064, ChinaCenter for Reproductive Medicine, Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, 250012, ChinaInstitute for Advanced Study, Shenzhen University, 518067, ChinaCenter for Translational Medicine, Precision Medicine Institute, The First Affiliated Hospital, Sun Yat-sen University, 510064, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 510064, ChinaInstitute for Advanced Study, Shenzhen University, 518067, ChinaLimbal stem cells are essential for continuous corneal regeneration and injury repair. METTL3-catalyzed N6-methyladenosine (m6A) mRNA modifications are involved in many biological processes and play a specific role in stem cell regeneration, while the role of m6A modifications in corneal injury repair remains unknown. In this study, we generated a limbal stem cell-specific METTL3 knockout mouse model and studied the role of m6A in repairing corneal injury caused by alkali burn. The results showed that METTL3 knockout in the limbal stem cells promotes the in vivo cell proliferation and migration, leading to the fast repair of corneal injury. In addition, m6A modification profiling identified stem cell regulatory factors AHNAK and DDIT4 as m6A targets. Our study reveals the essential functions of m6A RNA modification in regulating injury repair and provides novel insights for clinical therapy of corneal diseases.http://dx.doi.org/10.1155/2021/5512153
spellingShingle Yarong Dai
Maosheng Cheng
Siyan Zhang
Rongsong Ling
Jieqi Wen
Yifan Cheng
Boxuan Huang
Jinrong Li
Caifeng Dai
Shiqing Mao
Shuibin Lin
Huangxuan Shen
Yizhou Jiang
METTL3-Mediated m6A RNA Modification Regulates Corneal Injury Repair
Stem Cells International
title METTL3-Mediated m6A RNA Modification Regulates Corneal Injury Repair
title_full METTL3-Mediated m6A RNA Modification Regulates Corneal Injury Repair
title_fullStr METTL3-Mediated m6A RNA Modification Regulates Corneal Injury Repair
title_full_unstemmed METTL3-Mediated m6A RNA Modification Regulates Corneal Injury Repair
title_short METTL3-Mediated m6A RNA Modification Regulates Corneal Injury Repair
title_sort mettl3 mediated m6a rna modification regulates corneal injury repair
url http://dx.doi.org/10.1155/2021/5512153
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