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Cited by 11RNA modifications and cancerRNA and protein synthesis mechanismsRNA regulation and disease

N6-adenosine methylation controls the translation of insulin mRNA

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Wilinski, Daniel, Dus, Monica·2023·Nature Structural & Molecular Biology
DOI 10.1038/s41594-023-01048-xPMC PMC11756593

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Abstract

Control of insulin mRNA translation is crucial for energy homeostasis, but the mechanisms remain largely unknown. We discovered that insulin mRNAs across invertebrates, vertebrates and mammals feature the modified base N 6-methyladenosine (m 6 A). In flies, this RNA modification enhances insulin mRNA translation by promoting the association of the transcript with polysomes. Depleting m 6 A in Drosophila melanogaster insulin 2 mRNA (dilp2) directly through specific 3' untranslated region (UTR) mutations, or indirectly by mutating the m 6 A writer Mettl3, decreases dilp2 protein production, leading to aberrant energy homeostasis and diabetic-like phenotypes. Together, our findings reveal adenosine mRNA methylation as a key regulator of insulin protein synthesis with notable implications for energy balance and metabolic disease.

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  • m6A depletion via 3′UTR mutations of insulin mRNA or indirectly by mutating Mettl3 decreased insulin protein production, leading to aberrant homeostasis and diabetic-like phenotype.

    “Interestingly, m6A depletion via 3′UTR mutations of insulin mRNA or indirectly by mutating Mettl3 decreased insulin protein production, leading to aberrant homeostasis and diabetic-like phenotype (Wilinski and Dus 2023).”

    From METTL3 uncouples chromatin accessibility from transcription during retinal development (2025) · cites this paper as Wilinski and Dus 2023

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Cited by

Sorted by citations

Authors
Wilinski, D., & Dus, M.
Affiliations
University of Michigan (US)
Corresponding author
Dus, Monica
ORCID
Venue
Nature Structural & Molecular Biology
Publisher
Springer Science and Business Media LLC
Published
2023-07-24
Volume
30
Issue
9
Pages
1260-1264
ISSN
  • 1545-9985 (ISSN-L)
  • 1545-9993
DOI
10.1038/s41594-023-01048-x
PMC
PMC11756593
OpenAlex
W4385197368
Cited by
11
References
0
Citations by year
2026: 2 · 2025: 4 · 2024: 5
FWCI
0.98
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Structural & Molecular Biology (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Science Foundation (1941822, P30 DK089503, CAREER)
  • U.S. Department of Agriculture
  • KU Leuven
  • Université de Lausanne
  • National Institutes of Health (NIH T32, DK089503)
  • National Institute on Drug Abuse (T32DA007268)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DP2DK113750, K99DK128539, R00DK097141, P30DK089503)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
Keywords
N6-methyladenosine, m6A RNA methylation, DILP2, METTL3, 3' untranslated region, polysome association, energy homeostasis, diabetes mellitus, Drosophila melanogaster, mRNA methylation
MeSH terms
Adenosine, Animals, Drosophila melanogaster, Insulin, Mammals, Methylation, Methyltransferases, RNA, Messenger

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