Mettl5 mediated 18S rRNA N6-methyladenosine (m6A) modification controls stem cell fate determination and neural function

Lu Wang; Yu Liang; Rongzhi Lin; Qiuchan Xiong; Peng Yu; Jieyi Ma; Maosheng Cheng; Hui Han; Xiaochen Wang; Ganping Wang; Fengyin Liang; Zhong Pei; Demeng Chen; Quan Yuan; Yi-Zhou Jiang; Shuibin Lin

doi:10.1016/j.gendis.2020.07.004

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Mettl5 mediated 18S rRNA N6-methyladenosine (m6A) modification controls stem cell fate determination and neural function

Full-length article | 更新时间：2022-06-24

- Mettl5 mediated 18S rRNA N6-methyladenosine (m6A) modification controls stem cell fate determination and neural function
- Mettl5 mediated 18S rRNA N6-methyladenosine (m6A) modification controls stem cell fate determination and neural function
- Genes & Diseases 2022年9卷第1期
- 作者机构：
  
  1. Center for Translational Medicine, Precision Medicine Institute, The First Affiliated Hospital, Sun Yat-sen University,Guangdong,Guangzhou,PR China,510080
  2. Institute for Advanced Study, Shenzhen University,Guangdong,Shenzhen,PR China,518060
  3. Department of Otorhinolaryngology, The Second Affiliated Hospital of Fujian Medical University,Fujian,Quanzhou,PR China,362000
  4. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University,Sichuan,Chengdu,PR China,610041
  5. Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology,Guangdong,Guangzhou,PR China,510080
- 作者简介：
- 基金信息：
- DOI：10.1016/j.gendis.2020.07.004
  中图分类号：
- 纸质出版日期：2022，
  
  网络出版日期：2022-1-1，
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Lu Wang, Yu Liang, Rongzhi Lin, 等. Mettl5 mediated 18S rRNA N6-methyladenosine (m6A) modification controls stem cell fate determination and neural function[J]. Genes & Diseases, 2022,9(1).

Lu Wang, Yu Liang, Rongzhi Lin, et al. Mettl5 mediated 18S rRNA N6-methyladenosine (m6A) modification controls stem cell fate determination and neural function[J]. Genes & Diseases, 2022,9(1).
Lu Wang, Yu Liang, Rongzhi Lin, 等. Mettl5 mediated 18S rRNA N6-methyladenosine (m6A) modification controls stem cell fate determination and neural function[J]. Genes & Diseases, 2022,9(1). DOI： 10.1016/j.gendis.2020.07.004.

Lu Wang, Yu Liang, Rongzhi Lin, et al. Mettl5 mediated 18S rRNA N6-methyladenosine (m6A) modification controls stem cell fate determination and neural function[J]. Genes & Diseases, 2022,9(1). DOI： 10.1016/j.gendis.2020.07.004.

摘要

Abstract

Ribosome RNA (rRNA) accounts for more than 80% of the cell's total RNA

while the physiological functions of rRNA modifications are poorly understood. Mutations of 18S rRNA m

A methyltransferase METTL5 cause intellectual disability

microcephaly

and facial dysmorphisms in patients

however

little is known about the underlying mechanisms. In this study

we identified METTL5 protein complex and revealed that METTL5 mainly interacts with RNA binding proteins and ribosome proteins. Functionally

we found that Mettl5 knockout in mESCs leads to the abnormal craniofacial and nervous development. Moreover

using Mettl5 knockout mouse model

we further demonstrated that Mettl5 knockout mice exhibit intellectual disability

recapitulating the human phenotype. Mechanistically

we found that Mettl5 maintains brain function and intelligence by regulating the myelination process. Our study uncovered the causal correlation between mis-regulated 18S rRNA m

A modification and neural function defects

supporting the important physiological functions of rRNA modifications in human diseases.

关键词

Keywords

18S rRNAIntellectual disabilityMETTL5N6-methyladenosine (m6A)Neural development

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