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METTL1 Promotes let-7 MicroRNA Processing via m7G Methylation.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Bannister, Andrew J 
Andrews, Byron 

Abstract

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.

Description

Keywords

7-methylguanosine, G-quadruplexes, METTL1, RNA methylation, SAM-dependent methyltransferase, cell migration, high-throughput sequencing, let-7, miRNA biogenesis, microRNA, A549 Cells, Base Sequence, Biological Assay, Caco-2 Cells, Cell Movement, Cell Proliferation, Guanosine, HEK293 Cells, Humans, Methylation, Methyltransferases, MicroRNAs, Nucleic Acid Conformation, RNA Processing, Post-Transcriptional

Journal Title

Mol Cell

Conference Name

Journal ISSN

1097-2765
1097-4164

Volume Title

74

Publisher

Elsevier BV
Sponsorship
Kay Kendall Leukaemia Fund (KKL1103)
Cancer Research UK (17001)
Cancer Research Uk (None)
Cancer Research UK (C7/A18061)
European Research Council (268569)
Cancer Research UK (C6946/A24843)
Wellcome Trust (203144/Z/16/Z)