The DOI matches its Crossref record; 70 of the 70 references it cites were found in a registry or an index.
FTO controls reversible m6Am RNA methylation during snRNA biogenesis
Open accessAbstract
AbstractSmall nuclear RNAs (snRNAs) are core spliceosome components and mediate pre-mRNA splicing. Here we show that snRNAs contain a regulated and reversible nucleotide modification causing them to exist as two different methyl isoforms, m1 and m2, reflecting the methylation state of the adenosine adjacent to the snRNA cap. We find that snRNA biogenesis involves the formation of an initial m1 isoform with a single-methylated adenosine (2′-O-methyladenosine, Am), which is then converted to a dimethylated m2 isoform (N6,2′-O-dimethyladenosine, m6Am). The relative m1 and m2 isoform levels are determined by the RNA demethylase FTO, which selectively demethylates the m2 isoform. We show FTO is inhibited by the oncometabolite d-2-hydroxyglutarate, resulting in increased m2-snRNA levels. Furthermore, cells that exhibit high m2-snRNA levels show altered patterns of alternative splicing. Together, these data reveal that FTO controls a previously unknown central step of snRNA processing involving reversible methylation, and suggest that epitranscriptomic information in snRNA may influence mRNA splicing.Two different methylation states of the adenosine adjacent to the snRNA cap are found in the biogenesis process of snRNAs, Am and m6Am, whose levels are regulated by FTO and are related to alternative pre-mRNA splicing.
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Cites
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Cancer-associated IDH1 mutations produce 2-hydroxyglutarate
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Self-citationN6-Methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO
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Single-nucleotide-resolution mapping of m6A and m6Am throughout the transcriptome
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Cited by
Reading, writing and erasing mRNA methylation
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Self-citationRole of RNA modifications in cancer
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Crosstalk between epitranscriptomic and epigenetic mechanisms in gene regulation
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FTO mediates LINE1 m 6 A demethylation and chromatin regulation in mESCs and mouse development
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The role of m6A modification in physiology and disease
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Metadata
- Authors
- Mauer, J., Sindelar, M., Despic, V., Guez, T., Hawley, B. R., Vasseur, J.-J., Rentmeister, A., Gross, S. S., Pellizzoni, L., Debart, F., Goodarzi, H., & Jaffrey, S. R.
- Venue
- Nature Chemical Biology
- Published
- 2019-02-18
- Volume
- 15
- Issue
- 4
- Pages
- 340-347
- ISSN
- 1552-4450 (ISSN-L)
- 1552-4469
- OpenAlex
- W2912048746
- Cited by
- 268
- References
- 70
- FWCI
- 10.89
- Type
- journal article
- Language
- en
- Open access
- green
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- Mauer, J., Sindelar, M., Despic, V., Guez, T., Hawley, B. R., Vasseur, J.-J., Rentmeister, A., Gross, S. S., Pellizzoni, L., Debart, F., Goodarzi, H., & Jaffrey, S. R. (2019). FTO controls reversible m6Am RNA methylation during snRNA biogenesis. Nature Chemical Biology. https://doi.org/10.1038/s41589-019-0231-8
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