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Cited by 200RNA modifications and cancerRNA regulation and diseaseEpigenetics and DNA Methylation

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The role of m6A modification in physiology and disease

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Yang, Chuan, Hu, Yiyang, Zhou, Bo, Bao, Yulu, Li, Zhibin, Gong, Chunli, Yang, Huan, Wang, Sumin, Xiao, Yufeng·2020·Cell Death & Disease
DOI 10.1038/s41419-020-03143-zPMC PMC7649148
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Abstract

Similar to DNA epigenetic modifications, multiple reversible chemical modifications on RNAs have been uncovered in a new layer of epigenetic modification. N6-methyladenosine (m 6 A), a modification that occurs in ~30% transcripts, is dynamically regulated by writer complex (methylase) and eraser (RNA demethylase) proteins, and is recognized by reader (m 6 A-binding) proteins. The effects of m 6 A modification are reflected in the functional modulation of mRNA splicing, export, localization, translation, and stability by regulating RNA structure and interactions between RNA and RNA-binding proteins. This modulation is involved in a variety of physiological behaviors, including neurodevelopment, immunoregulation, and cellular differentiation. The disruption of m 6 A modulations impairs gene expression and cellular function and ultimately leads to diseases such as cancer, psychiatric disorders, and metabolic disease. This review focuses on the mechanisms and functions of m 6 A modification in a variety of physiological behaviors and diseases.

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Fig. 1 The regulation of m6A modification. M6A is added, removed and recognized by its writers, erasers and readers. METTL3-METTL14 is the core of the methyltransferase and functions in cellular m6A deposition on nuclear RNAs. WTAP is a subunit of the methyltransferase, which promotes the recruitment of the m6A methyltransferase complex to mRNA targets. KIAA1429 and RBM15 (RNA binding motif protein 15) are also required for the above process. FTO and ALKBH5 are two enzymes capable of removing m6A, exhibiting efficient oxidative demethylation activity of abundant m6A in RNA. YTH domain family, HNRNP protein family, IGF2BPs and eIF3 bind to m6A-modified RNA through conserved m6A-binding domains and play different roles in RNA metabolism.
Fig. 1 The regulation of m6A modification. M6A is added, removed and recognized by its writers, erasers and readers. METTL3-METTL14 is the core of the methyltransferase and functions in cellular m6A deposition on nuclear RNAs. WTAP is a subunit of the methyltransferase, which promotes the recruitment of the m6A methyltransferase complex to mRNA targets. KIAA1429 and RBM15 (RNA binding motif protein 15) are also required for the above process. FTO and ALKBH5 are two enzymes capable of removing m6A, exhibiting efficient oxidative demethylation activity of abundant m6A in RNA. YTH domain family, HNRNP protein family, IGF2BPs and eIF3 bind to m6A-modified RNA through conserved m6A-binding domains and play different roles in RNA metabolism.CC BY · PubMed Central
Fig. 2 The role of m6A in different cancers. M6A plays diverse roles in different cancer, and even plays the opposite roles in a type of cancer. On the on hand, m6A promotes tumor progression by increasing oncogene expression and decreasing tumor suppressor gene expression. On the other hand, m6A suppresses tumor progression in opposite ways. Specific functions of m6A in the main text.
Fig. 2 The role of m6A in different cancers. M6A plays diverse roles in different cancer, and even plays the opposite roles in a type of cancer. On the on hand, m6A promotes tumor progression by increasing oncogene expression and decreasing tumor suppressor gene expression. On the other hand, m6A suppresses tumor progression in opposite ways. Specific functions of m6A in the main text.CC BY · PubMed Central

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Metadata

Authors
Yang, C., Hu, Y., Zhou, B., Bao, Y., Li, Z., Gong, C., Yang, H., Wang, S., & Xiao, Y.
Affiliations
Army Medical University (CN)
Corresponding author
  • Wang, Sumin
  • Xiao, Yufeng
ORCID
Venue
Cell Death & Disease
Publisher
Springer Science and Business Media LLC
Published
2020-11-08
Volume
11
Issue
11
Pages
960-960
ISSN
2041-4889 (ISSN-L)
DOI
10.1038/s41419-020-03143-z
PMC
PMC7649148
OpenAlex
W3099680336
Cited by
200
References
156
Citations by year
2026: 21 · 2025: 40 · 2024: 34 · 2023: 39 · 2022: 39 · 2021: 26 · 2020: 1
FWCI
2.51
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Death and Disease (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Chongqing Science and Technology Commission (cstc2015jcyjBX0021, cstc2017jcyjAX0421)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
N6-methyladenosine, RNA methylation, epitranscriptomics, m6A writer complex, m6A erasers, m6A reader proteins, mRNA splicing, mRNA stability, translational regulation, RNA localization, RNA-binding proteins, brain development, immune regulation, cell differentiation, cancer, mental illness, metabolic disorders
MeSH terms
Adenosine, Animals, Mental Disorders, Gene Expression Regulation, Humans, Metabolic Diseases, Neoplasms, RNA, Messenger, DNA Methylation, Epigenesis, Genetic

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CoChat. (2026). Citation check: The role of m6A modification in physiology and disease. https://app.cochat.ai/papers/10.1038/s41419-020-03143-z
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Yang, C., Hu, Y., Zhou, B., Bao, Y., Li, Z., Gong, C., Yang, H., Wang, S., & Xiao, Y. (2020). The role of m6A modification in physiology and disease. Cell Death & Disease. https://doi.org/10.1038/s41419-020-03143-z