N6-methyladenosine reader YTHDF family in biological processes: Structures, roles, and mechanisms

Lin Chen; Yang Gao; Simiao Xu; Jinxiong Yuan; Min Wang; Tianyu Li; Jun Gong

doi:10.3389/fimmu.2023.1162607

N6-methyladenosine reader YTHDF family in biological processes: Structures, roles, and mechanisms

Front Immunol. 2023 Mar 14:14:1162607. doi: 10.3389/fimmu.2023.1162607. eCollection 2023.

Authors

Lin Chen¹, Yang Gao¹, Simiao Xu², Jinxiong Yuan¹, Min Wang¹, Tianyu Li³, Jun Gong¹

Affiliations

¹ Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Division of Endocrinology, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Branch of National Clinical Research Center for Metabolic Disease, Wuhan, China.
³ Trauma Center/Department of Emergency and Traumatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Abstract

As the most abundant and conserved internal modification in eukaryote RNAs, N6-methyladenosine (m⁶A) is involved in a wide range of physiological and pathological processes. The YT521-B homology (YTH) domain-containing family proteins (YTHDFs), including YTHDF1, YTHDF2, and YTHDF3, are a class of cytoplasmic m⁶A-binding proteins defined by the vertebrate YTH domain, and exert extensive functions in regulating RNA destiny. Distinct expression patterns of the YTHDF family in specific cell types or developmental stages result in prominent differences in multiple biological processes, such as embryonic development, stem cell fate, fat metabolism, neuromodulation, cardiovascular effect, infection, immunity, and tumorigenesis. The YTHDF family mediates tumor proliferation, metastasis, metabolism, drug resistance, and immunity, and possesses the potential of predictive and therapeutic biomarkers. Here, we mainly summary the structures, roles, and mechanisms of the YTHDF family in physiological and pathological processes, especially in multiple cancers, as well as their current limitations and future considerations. This will provide novel angles for deciphering m⁶A regulation in a biological system.

Keywords: M6A; YTHDF; biological process; cancer; clinical applications.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

RNA* / metabolism
RNA-Binding Proteins* / genetics
RNA-Binding Proteins* / metabolism

Substances

RNA-Binding Proteins
RNA

Grants and funding

This study was supported by grants from the National Natural Science Foundation of China (81900518 to JG; 81702792 to SX; 82000088 to TL); the HUBEI Natural Science Foundation (2017CFB467 to MW); Tongji Hospital Clinical Research Flagship Program (grant no. 2019CR203), National Key Research and Development Program of China (grant no. 2022YFA110530 and 2019TFC1315905).