Advances in mRNA 5-methylcytosine modifications: Detection, effectors, biological functions, and clinical relevance

Gangqiang Guo; Kan Pan; Su Fang; Lele Ye; Xinya Tong; Zhibin Wang; Xiangyang Xue; Huidi Zhang

doi:10.1016/j.omtn.2021.08.020

Advances in mRNA 5-methylcytosine modifications: Detection, effectors, biological functions, and clinical relevance

Mol Ther Nucleic Acids. 2021 Aug 26:26:575-593. doi: 10.1016/j.omtn.2021.08.020. eCollection 2021 Dec 3.

Authors

Gangqiang Guo¹, Kan Pan², Su Fang¹, Lele Ye³, Xinya Tong¹, Zhibin Wang¹, Xiangyang Xue¹, Huidi Zhang⁴

Affiliations

¹ Wenzhou Collaborative Innovation Center of Gastrointestinal Cancer in Basic Research and Precision Medicine, Wenzhou Key Laboratory of Cancer-related Pathogens and Immunity, Department of Microbiology and Immunology, Institute of Molecular Virology and Immunology, Institute of Tropical Medicine, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, China.
² First Clinical College, Wenzhou Medical University, Wenzhou, China.
³ Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
⁴ Department of Nephrology, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China.

Abstract

5-methylcytosine (m⁵C) post-transcriptional modifications affect the maturation, stability, and translation of the mRNA molecule. These modifications play an important role in many physiological and pathological processes, including stress response, tumorigenesis, tumor cell migration, embryogenesis, and viral replication. Recently, there has been a better understanding of the biological implications of m⁵C modification owing to the rapid development and optimization of detection technologies, including liquid chromatography-tandem mass spectrometry (LC-MS/MS) and RNA-BisSeq. Further, predictive models (such as PEA-m⁵C, m⁵C-PseDNC, and DeepMRMP) for the identification of potential m⁵C modification sites have also emerged. In this review, we summarize the current experimental detection methods and predictive models for mRNA m⁵C modifications, focusing on their advantages and limitations. We systematically surveyed the latest research on the effectors related to mRNA m⁵C modifications and their biological functions in multiple species. Finally, we discuss the physiological effects and pathological significance of m⁵C modifications in multiple diseases, as well as their therapeutic potential, thereby providing new perspectives for disease treatment and prognosis.

Keywords: 5-methylcytosine; RNA epigenetics; disease; mRNA; post-transcriptional modification; prediction.

Publication types

Review