The DOI matches its Crossref record; 66 of the 66 references it cites were found in a registry or an index.
METTL1 Promotes let-7 MicroRNA Processing via m7G Methylation
Open accessAbstract
7-methylguanosine (m7G) is present at mRNA caps and at defined internal positions within tRNAs and rRNAs. However, its detection within low-abundance mRNAs and microRNAs (miRNAs) has been hampered by a lack of sensitive detection strategies. Here, we adapt a chemical reactivity assay to detect internal m7G in miRNAs. Using this technique (Borohydride Reduction sequencing [BoRed-seq]) alongside RNA immunoprecipitation, we identify m7G within a subset of miRNAs that inhibit cell migration. We show that the METTL1 methyltransferase mediates m7G methylation within miRNAs and that this enzyme regulates cell migration via its catalytic activity. Using refined mass spectrometry methods, we map m7G to a single guanosine within the let-7e-5p miRNA. We show that METTL1-mediated methylation augments let-7 miRNA processing by disrupting an inhibitory secondary structure within the primary miRNA transcript (pri-miRNA). These results identify METTL1-dependent N7-methylation of guanosine as a new RNA modification pathway that regulates miRNA structure, biogenesis, and cell migration.
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“Furthermore, the ubiquitin-like domain within the ligase promotes ubiquitination of histone H3, which recruits DNMT1 to newly replicated chromatin to ensure the inheritance of DNA methylation 42 .”
From The roles of DNA, RNA and histone methylation in ageing and cancer (2019) · cites this paper as [42]
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Metadata
- Authors
- Pandolfini, L., Barbieri, I., Bannister, A. J., Hendrick, A., Andrews, B., Webster, N., Murat, P., Mach, P., Brandi, R., Robson, S. C., Migliori, V., Alendar, A., d’Onofrio, M., Balasubramanian, S., & Kouzarides, T.
- Affiliations
- University of Cambridge (GB)
- European Brain Research Institute (IT)
- Istituto di Farmacologia Traslazionale (IT)
- Corresponding author
- Kouzarides, Tony
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2019-06
- Volume
- 74
- Issue
- 6
- Pages
- 1278-1290.e9
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC6591002
- OpenAlex
- W2941132662
- Cited by
- 491
- References
- 66
- Citations by year
- 2026: 32 · 2025: 68 · 2024: 76 · 2023: 95 · 2022: 101 · 2021: 68 · 2020: 37 · 2019: 14
- FWCI
- 18.36
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by-nc-nd)
- Apollo
- Funders
- European Research Council (268569)
- Cancer Research UK (RG72100)
- Horizon 2020 (732678)
- Wellcome Trust (WT203144, C6946/A24843)
- Kay Kendall Leukaemia Fund (337778, RG86786, RG88664)
- 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 › Cancer Research › MicroRNA in disease regulation
- Keywords
- METTL1, let-7 microRNA, 7-methylguanosine, RNA methylation, microRNA biogenesis, cell migration, RNA modification
- MeSH terms
- A549 Cells, Base Sequence, Biological Assay, Cell Movement, Guanosine, Humans, Methylation, Methyltransferases, Nucleic Acid Conformation, RNA Processing, Post-Transcriptional, Caco-2 Cells, MicroRNAs, Cell Proliferation, HEK293 Cells
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