METTL1 Promotes let-7 MicroRNA Processing via m7G Methylation.
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Authors
Andrews, Byron
Webster, Natalie
Murat, Pierre
Mach, Pia
Brandi, Rossella
Robson, Samuel C
Migliori, Valentina
Alendar, Andrej
d'Onofrio, Mara
Publication Date
2019-06Journal Title
Molecular cell
ISSN
1097-2765
Publisher
Cell Press
Volume
74
Issue
6
Pages
1278-1290.e9
Language
eng
Type
Article
This Version
AM
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Pandolfini, L., Barbieri, I., Bannister, A., Hendrick, A., Andrews, B., Webster, N., Murat, P., et al. (2019). METTL1 Promotes let-7 MicroRNA Processing via m7G Methylation.. Molecular cell, 74 (6), 1278-1290.e9. https://doi.org/10.1016/j.molcel.2019.03.040
Abstract
N7-methylation of guanosine (m7G) occurs 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 lack of sensitive detection strategies. Here, we adapt a chemical reactivity assay to detect internal m7G in miRNA. Using this technique (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 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.
Keywords
Caco-2 Cells, Humans, Methyltransferases, MicroRNAs, Guanosine, Biological Assay, Cell Proliferation, Cell Movement, RNA Processing, Post-Transcriptional, Base Sequence, Nucleic Acid Conformation, Methylation, HEK293 Cells, A549 Cells
Sponsorship
Kay Kendall Leukaemia Fund (KKL1103)
Cancer Research UK (17001)
Cancer Research UK (10827)
Cancer Research UK (C7/A18061)
European Research Council (268569)
Cancer Research UK (C6946/A24843)
Wellcome Trust (203144/Z/16/Z)
Identifiers
External DOI: https://doi.org/10.1016/j.molcel.2019.03.040
This record's URL: https://www.repository.cam.ac.uk/handle/1810/291242
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International
Licence URL: https://creativecommons.org/licenses/by-nc-nd/4.0/