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METTL1 Promotes let-7 MicroRNA Processing via m7G Methylation.

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cam.issuedOnline2019-04-25
cam.orpheus.successThu Jan 30 10:47:35 GMT 2020 - Embargo updated
dc.contributor.authorPandolfini, Luca
dc.contributor.authorBarbieri, Isaia
dc.contributor.authorBannister, Andrew J
dc.contributor.authorHendrick, Alan
dc.contributor.authorAndrews, Byron
dc.contributor.authorWebster, Natalie
dc.contributor.authorMurat, Pierre
dc.contributor.authorMach, Pia
dc.contributor.authorBrandi, Rossella
dc.contributor.authorRobson, Samuel C
dc.contributor.authorMigliori, Valentina
dc.contributor.authorAlendar, Andrej
dc.contributor.authord'Onofrio, Mara
dc.contributor.authorBalasubramanian, Shankar
dc.contributor.authorKouzarides, Tony
dc.contributor.orcidPandolfini, Luca [0000-0003-1444-8167]
dc.contributor.orcidBarbieri, Isaia [0000-0003-3035-8970]
dc.contributor.orcidBannister, Andrew [0000-0002-6312-4436]
dc.contributor.orcidHendrick, Alan [0000-0002-8604-0462]
dc.contributor.orcidBalasubramanian, Shankar [0000-0002-0281-5815]
dc.contributor.orcidKouzarides, Tony [0000-0002-8918-4162]
dc.date.accessioned2019-04-05T23:31:47Z
dc.date.available2019-04-05T23:31:47Z
dc.date.issued2019-06-20
dc.description.abstract7-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.
dc.format.mediumPrint-Electronic
dc.identifier.doi10.17863/CAM.38421
dc.identifier.eissn1097-4164
dc.identifier.issn1097-2765
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/291242
dc.languageeng
dc.language.isoeng
dc.publisherElsevier BV
dc.publisher.urlhttp://dx.doi.org/10.1016/j.molcel.2019.03.040
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject7-methylguanosine
dc.subjectG-quadruplexes
dc.subjectMETTL1
dc.subjectRNA methylation
dc.subjectSAM-dependent methyltransferase
dc.subjectcell migration
dc.subjecthigh-throughput sequencing
dc.subjectlet-7
dc.subjectmiRNA biogenesis
dc.subjectmicroRNA
dc.subjectA549 Cells
dc.subjectBase Sequence
dc.subjectBiological Assay
dc.subjectCaco-2 Cells
dc.subjectCell Movement
dc.subjectCell Proliferation
dc.subjectGuanosine
dc.subjectHEK293 Cells
dc.subjectHumans
dc.subjectMethylation
dc.subjectMethyltransferases
dc.subjectMicroRNAs
dc.subjectNucleic Acid Conformation
dc.subjectRNA Processing, Post-Transcriptional
dc.titleMETTL1 Promotes let-7 MicroRNA Processing via m7G Methylation.
dc.typeArticle
dcterms.dateAccepted2019-03-27
prism.endingPage1290.e9
prism.issueIdentifier6
prism.publicationDate2019
prism.publicationNameMol Cell
prism.startingPage1278
prism.volume74
pubs.funder-project-idKay Kendall Leukaemia Fund (KKL1103)
pubs.funder-project-idCancer Research UK (17001)
pubs.funder-project-idCancer Research Uk (None)
pubs.funder-project-idCancer Research UK (C7/A18061)
pubs.funder-project-idEuropean Research Council (268569)
pubs.funder-project-idCancer Research UK (C6946/A24843)
pubs.funder-project-idWellcome Trust (203144/Z/16/Z)
rioxxterms.licenseref.startdate2019-06
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review
rioxxterms.versionAM
rioxxterms.versionofrecord10.1016/j.molcel.2019.03.040

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