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Cited by 164RNA modifications and cancerRNA regulation and diseaseRNA and protein synthesis mechanisms

The proteins of mRNA modification: writers, readers, and erasers

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Flamand, Mathieu N., Tegowski, Matthew, Meyer, Kate D.·2023·Annual Review of Biochemistry
DOI 10.1146/annurev-biochem-052521-035330PMC PMC10443600
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Abstract

Over the past decade, mRNA modifications have emerged as important regulators of gene expression control in cells. Fueled in large part by the development of tools for detecting RNA modifications transcriptome wide, researchers have uncovered a diverse epitranscriptome that serves as an additional layer of gene regulation beyond simple RNA sequence. Here, we review the proteins that write, read, and erase these marks, with a particular focus on the most abundant internal modification, N 6 -methyladenosine (m 6 A). We first describe the discovery of the key enzymes that deposit and remove m 6 A and other modifications and discuss how our understanding of these proteins has shaped our views of modification dynamics. We then review current models for the function of m 6 A reader proteins and how our knowledge of these proteins has evolved. Finally, we highlight important future directions for the field and discuss key questions that remain unanswered.

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  • The m6A modification occurs in all types of RNA, although it has the lowest abundance in tRNA.

    “The m6A modification occurs in all types of RNA, although it has the lowest abundant in tRNA (Linder et al., 2015; Flamand et al., 2023).”

    From β-amyloid accumulation enhances microtubule associated protein tau pathology in an APPNL-G-F/MAPTP301S mouse model of Alzheimer’s disease (2024) · cites this paper as Flamand et al., 2023

    The Introduction reports m6A in mRNA, and the section on m6A recognition by the YTH domain identifies m6A sites in 18S and 28S rRNA (pages unavailable). The review does not establish that m6A occurs in all RNA types or that its abundance is lowest in tRNA; its discussion of tRNA in ‘Writers of other mRNA modifications’ concerns other modifications. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • m6Am non-enzymatically converts to m6A.

    “Interestingly, m6Am also non-enzymatically converts to m6A, so the biological impact of m6Am is currently ambiguous (Linder et al., 2015; Flamand et al., 2023).”

    From β-amyloid accumulation enhances microtubule associated protein tau pathology in an APPNL-G-F/MAPTP301S mouse model of Alzheimer’s disease (2024) · cites this paper as Flamand et al., 2023

    The “Writers of other mRNA modifications” section describes enzymatic formation of m6Am by PCIF1 and uncertainty about m6Am’s biological effects. It does not address non-enzymatic conversion of m6Am to m6A; searches for that conversion and its proposed mechanism found no passage stating it. (LLM, conf=0.74)

    Experimental — accuracy not yet measured

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References 208 · Cited by 164

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Authors
Flamand, M. N., Tegowski, M., & Meyer, K. D.
Affiliations
Duke University (US)
Corresponding author
Meyer, Kate D.
ORCID
Venue
Annual Review of Biochemistry
Publisher
Annual Reviews
Published
2023-06-20
Volume
92
Issue
1
Pages
145-173
ISSN
  • 0066-4154 (ISSN-L)
  • 1545-4509
DOI
10.1146/annurev-biochem-052521-035330
PMC
PMC10443600
OpenAlex
W4366138140
Cited by
164
References
208
Citations by year
2026: 39 · 2025: 57 · 2024: 51 · 2023: 16 · 2012: 1
FWCI
4.31
Type
journal article
Language
en
Open access
Licence
Locations
  • Annual Review of Biochemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Rita Allen Foundation
  • National Institutes of Health
  • National Institute of Mental Health (R00MH104712, R01MH118366)
  • National Institute on Drug Abuse (DP1DA046584)
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 › RNA and protein synthesis mechanisms
Keywords
mRNA modification, epitranscriptome, N6-methyladenosine, m6A writers, m6A erasers, m6A reader, RNA-modifying enzymes, gene expression regulation
MeSH terms
Adenosine, Gene Expression Regulation, Proteins, RNA, Messenger, Transcriptome

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