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Regulatory roles of N6-methyladenosine (m6A) methylation in RNA processing and non-communicable diseases

Abstract

Post-transcriptional RNA modification is an emerging epigenetic control mechanism in cells that is important in many different cellular and organismal processes. N6-methyladenosine (m6A) is one of the most prevalent, prolific, and ubiquitous internal transcriptional alterations in eukaryotic mRNAs, making it an important topic in the field of Epigenetics. m6A methylation acts as a dynamical regulatory process that regulates the activity of genes and participates in multiple physiological processes, by supporting multiple aspects of essential mRNA metabolic processes, including pre-mRNA splicing, nuclear export, translation, miRNA synthesis, and stability. Extensive research has linked aberrations in m6A modification and m6A-associated proteins to a wide range of human diseases. However, the impact of m6A on mRNA metabolism and its pathological connection between m6A and other non-communicable diseases, including cardiovascular disease, neurodegenerative disorders, liver diseases, and cancer remains in fragmentation. Here, we review the existing understanding of the overall role of mechanisms by which m6A exerts its activities and address new discoveries that highlight m6A’s diverse involvement in gene expression regulation. We discuss m6A deposition on mRNA and its consequences on degradation, translation, and transcription, as well as m6A methylation of non-coding chromosomal-associated RNA species. This study could give new information about the molecular process, early detection, tailored treatment, and predictive evaluation of human non-communicable diseases like cancer. We also explore more about new data that suggests targeting m6A regulators in diseases may have therapeutic advantages.

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Fig. 1: An overview of N6 -methyladenosine (m6 A) and m6 A-associated enzymes.
Fig. 2: N6-methyladenosine (m6A) cellular and molecular functions.
Fig. 3: m6A on chromosome-associated regulatory RNA regulates chromatin state and transcription.
Fig. 4: m6A modulators involved in human diseases.
Fig. 5: The molecular mechanisms of m6A modification in cancers.
Fig. 6: The role of m6A RNA modification in human cancer.

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All data generated or analyzed during this study are included in this published article.

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Funding

This work was supported by the National Natural Science Foundation of China (No. 31371386).

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FAK conducted research and drafted the original manuscript. FAK, BN, and UAA assisted in the process of revising the manuscript and figures and tables construction. FAK, SJ, and JD contributed to the conceptual framework. SJ, XYJ, and JD supervised the study and revised the manuscript. All authors listed have made a substantial, direct, and intellectual contribution to the work and have been approved for publication.

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Correspondence to Faiz Ali Khan, Xin-Ying Ji, Shaoping Ji or Jingcheng Dong.

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Khan, F.A., Nsengimana, B., Awan, U.A. et al. Regulatory roles of N6-methyladenosine (m6A) methylation in RNA processing and non-communicable diseases. Cancer Gene Ther (2024). https://doi.org/10.1038/s41417-024-00789-1

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