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N6-Methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO
Open accessAbstract
We report here that fat mass and obesity-associated protein (FTO) has efficient oxidative demethylation activity targeting the abundant N6-methyladenosine (m(6)A) residues in RNA in vitro. FTO knockdown with siRNA led to increased amounts of m(6)A in mRNA, whereas overexpression of FTO resulted in decreased amounts of m(6)A in human cells. We further show the partial colocalization of FTO with nuclear speckles, which supports the notion that m(6)A in nuclear RNA is a major physiological substrate of FTO.
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“The m6A modification can be removed by erasers, mainly FTO and ALKBH5 [24,25].”
From IMPlications of IMP2 in RNA Biology and Disease (2025) · cites this paper as [24]
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“Although evidence points to an oncogenic role of FTO in AML 15 ,”
From The roles of DNA, RNA and histone methylation in ageing and cancer (2019) · cites this paper as [15]
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“In addition to TET enzymes, D2HG can inhibit the N6-methyladenosine (m6A) RNA demethylase fat mass and obesity associated protein (FTO), another α -KG-dependent dioxygenase 15 .”
From The roles of DNA, RNA and histone methylation in ageing and cancer (2019) · cites this paper as [15]
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The roles and implications of RNA m6A modification in cancer
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Self-citationMechanism and Function of Oxidative Reversal of DNA and RNA Methylation
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“Previous studies reported that m 6 A RNA methylation is a dynamic reversible phenomenon (12,13) in which the METTL3-METTL14-WTAP complex works as m 6 A writers; fat mass-and obesity-associated protein (FTO) and AlkB homolog 5 (ALKBH5) demethylate as m 6 A erasers (12,13); and YTH domain family and…”
Transfer RNA demethylase ALKBH3 promotes cancer progression via induction of tRNA-derived small RNAs
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Self-citationYthdf2-mediated m6A mRNA clearance modulates neural development in mice
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A novel m6A reader Prrc2a controls oligodendroglial specification and myelination
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“Polyclonal rabbit anti-FTO antibody was affinity-purified from rabbits immunized with 6 × His tagged full-length human FTO protein as previously reported.(5) Polyclonal rabbit anti-ALKBH5 antibody was generated against synthesized peptide by CWBio (Beijing) as previously reported.”
MethodSelf-citationSpeeding with control: codon usage, tRNAs, and ribosomes
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Nuclear hnRNPA2B1 initiates and amplifies the innate immune response to DNA viruses
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N6-methyladenosine–encoded epitranscriptomics
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Self-citationCross-talk among writers, readers, and erasers of m 6 A regulates cancer growth and progression
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Self-citationEmerging Roles of RNA Modification: m6A and U-Tail
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Programmable m6A modification of cellular RNAs with a Cas13-directed methyltransferase
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The role of N6-methyladenosine (m6A) modification in the regulation of circRNAs
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“Fat mass and obesity-associated protein (FTO), the first protein identified to catalyse m(6)A demethylation [29], works together with a homologue of itself (ALKBH5, [30] to maintain the balance of m(6)A levels in the transcriptome [31].”
Background
Metadata
- Authors
- Jia, G., Fu, Y., Zhao, X., Dai, Q., Zheng, G., Yang, Y., Yi, C., Lindahl, T., Pan, T., Yang, Y.-G., & He, C.
- Affiliations
- University of Chicago (US)
- Chinese Academy of Sciences (CN)
- Cancer Research UK (GB)
- Corresponding author
- He, Chuan
- Venue
- Nature Chemical Biology
- Published
- 2011-10-16
- Volume
- 7
- Issue
- 12
- Pages
- 885-887
- ISSN
- 1552-4450 (ISSN-L)
- 1552-4469
- PMC
- PMC3218240
- OpenAlex
- W2071930821
- Cited by
- 4,106
- References
- 27
- Citations by year
- 2026: 272 · 2025: 416 · 2024: 473 · 2023: 489 · 2022: 546 · 2021: 544 · 2020: 341 · 2019: 217 · 2018: 218 · 2017: 159 · 2016: 109 · 2015: 107 · 2014: 94 · 2013: 67 · 2012: 45
- FWCI
- 26.98
- Type
- journal article
- Language
- en
- Update notices
- erratum (2012-11-26)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Chemical Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (GM071440, R01GM071440, R01GM088599, GM088599)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Keywords
- N6-methyladenosine, m6A demethylation, FTO, nuclear RNA, RNA modification, oxidative demethylation, nuclear speckles, obesity, RNA metabolism
- MeSH terms
- Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Adenosine, Cell Nucleus, HeLa Cells, Humans, Methylation, Obesity, Oxidation-Reduction, Proteins, RNA, Messenger, Substrate Specificity
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