Decoding m6A mRNA methylation by reader proteins in liver diseases

Lijiao Sun; Xin Chen; Sai Zhu; Jianan Wang; Shaoxi Diao; Jinyu Liu; Jinjin Xu; Xiaofeng Li; Yingyin Sun; Cheng Huang; Xiaoming Meng; Xiongwen Lv; Jun Li

doi:10.1016/j.gendis.2023.02.054

Decoding m⁶A mRNA methylation by reader proteins in liver diseases

Genes Dis. 2023 Apr 13;11(2):711-726. doi: 10.1016/j.gendis.2023.02.054. eCollection 2024 Mar.

Authors

Lijiao Sun^{1

2

3}, Xin Chen^{1

2

3}, Sai Zhu^{1

4}, Jianan Wang^{1

2}, Shaoxi Diao^{1

2

3}, Jinyu Liu^{1

2

3}, Jinjin Xu^{1

2

3}, Xiaofeng Li^{1

2}, Yingyin Sun^{1

5}, Cheng Huang^{1

2

3}, Xiaoming Meng^{1

2}, Xiongwen Lv^{1

2

3}, Jun Li^{1

2

3}

Affiliations

¹ Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, Anhui 230032, China.
² The Key Laboratory of Anti-inflammatory and Immune Medicines, Anhui Medical University, Ministry of Education, Hefei, Anhui 230032, China.
³ Institute for Liver Diseases of Anhui Medical University, ILD-AMU, Anhui Medical University, Hefei, Anhui 230032, China.
⁴ Department of Nephropathy, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China.
⁵ Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, China.

Abstract

N6-methyladenosine (m⁶A) is a dynamic and reversible epigenetic regulation. As the most prevalent internal post-transcriptional modification in eukaryotic RNA, it participates in the regulation of gene expression through various mechanisms, such as mRNA splicing, nuclear export, localization, translation efficiency, mRNA stability, and structural transformation. The involvement of m6A in the regulation of gene expression depends on the specific recognition of m6A-modified RNA by reader proteins. In the pathogenesis and treatment of liver disease, studies have found that the expression levels of key genes that promote or inhibit the development of liver disease are regulated by m⁶A modification, in which abnormal expression of reader proteins determines the fate of these gene transcripts. In this review, we introduce m⁶A readers, summarize the recognition and regulatory mechanisms of m⁶A readers on mRNA, and focus on the biological functions and mechanisms of m⁶A readers in liver cancer, viral hepatitis, non-alcoholic fatty liver disease (NAFLD), hepatic fibrosis (HF), acute liver injury (ALI), and other liver diseases. This information is expected to be of high value to researchers deciphering the links between m⁶A readers and human liver diseases.

Keywords: IGF2BPs; Liver diseases; YTH domain protein; m6A modification; m6A reader; mRNA metabolism.

Publication types

Review