Detailed resume of RNA m6A demethylases

Dandan Shen; Bo Wang; Ya Gao; Lijuan Zhao; Yaping Bi; Jinge Zhang; Ning Wang; Huiqin Kang; Jingru Pang; Ying Liu; Luping Pang; Zhe-Sheng Chen; Yi-Chao Zheng; Hong-Min Liu

doi:10.1016/j.apsb.2022.01.003

Detailed resume of RNA m⁶A demethylases

Acta Pharm Sin B. 2022 May;12(5):2193-2205. doi: 10.1016/j.apsb.2022.01.003. Epub 2022 Jan 11.

Authors

Dandan Shen^{1

2}, Bo Wang^{1

2}, Ya Gao^{1

2}, Lijuan Zhao^{1

2

3}, Yaping Bi^{1

2}, Jinge Zhang^{1

2}, Ning Wang⁴, Huiqin Kang^{1

2}, Jingru Pang^{1

2}, Ying Liu^{1

2}, Luping Pang^{1

2}, Zhe-Sheng Chen⁵, Yi-Chao Zheng^{1

2

3}, Hong-Min Liu^{1

2

3}

Affiliations

¹ Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, Zhengzhou 450052, China.
² Key Laboratory of Henan Province for Drug Quality and Evaluation, Institute of Drug Discovery and Development, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450052, China.
³ State Key Laboratory of Esophageal Cancer Prevention & Treatment, Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450052, China.
⁴ The School of Chinese Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
⁵ Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA.

Abstract

N6-Methyladenosine (m⁶A) is the most abundant internal modification in eukaryotic mRNA, playing critical role in various bioprocesses. Like other epigenetic modifications, m⁶A modification can be catalyzed by the methyltransferase complex and erased dynamically to maintain cells homeostasis. Up to now, only two m⁶A demethylases have been reported, fat mass and obesity-associated protein (FTO) and alkylation protein AlkB homolog 5 (ALKBH5), involving in a wide range of mRNA biological progress, including mRNA shearing, export, metabolism and stability. Furthermore, they participate in many significantly biological signaling pathway, and contribute to the progress and development of cancer along with other diseases. In this review, we focus on the studies about structure, inhibitors development and biological function of FTO and ALKBH5.

Keywords: ALKBH5; Diseases; FTO; Inhibitors; RNA demethylation; Screening.

Publication types

Review