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dc.contributor.authorNavarro, Isabela Cunha
dc.contributor.authorTuorto, Francesca
dc.contributor.authorJordan, David
dc.contributor.authorLegrand, Carine
dc.contributor.authorPrice, Jonathan
dc.contributor.authorBraukmann, Fabian
dc.contributor.authorHendrick, Alan G
dc.contributor.authorAkay, Alper
dc.contributor.authorKotter, Annika
dc.contributor.authorHelm, Mark
dc.contributor.authorLyko, Frank
dc.contributor.authorMiska, Eric A
dc.date.accessioned2020-11-13T00:30:34Z
dc.date.available2020-11-13T00:30:34Z
dc.date.issued2021-03-15
dc.identifier.issn0261-4189
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/312830
dc.description.abstractMethylation of carbon-5 of cytosines (m5 C) is a post-transcriptional nucleotide modification of RNA found in all kingdoms of life. While individual m5 C-methyltransferases have been studied, the impact of the global cytosine-5 methylome on development, homeostasis and stress remains unknown. Here, using Caenorhabditis elegans, we generated the first organism devoid of m5 C in RNA, demonstrating that this modification is non-essential. Using this genetic tool, we determine the localisation and enzymatic specificity of m5 C sites in the RNome in vivo. We find that NSUN-4 acts as a dual rRNA and tRNA methyltransferase in C. elegans mitochondria. In agreement with leucine and proline being the most frequently methylated tRNA isoacceptors, loss of m5 C impacts the decoding of some triplets of these two amino acids, leading to reduced translation efficiency. Upon heat stress, m5 C loss leads to ribosome stalling at UUG triplets, the only codon translated by an m5 C34-modified tRNA. This leads to reduced translation efficiency of UUG-rich transcripts and impaired fertility, suggesting a role of m5 C tRNA wobble methylation in the adaptation to higher temperatures.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherEMBO
dc.rightsAll rights reserved
dc.titleTranslational adaptation to heat stress is mediated by RNA 5-methylcytosine in Caenorhabditis elegans.
dc.typeArticle
prism.issueIdentifier6
prism.publicationDate2021
prism.publicationNameEMBO J
prism.startingPagee105496
prism.volume40
dc.identifier.doi10.17863/CAM.59928
dcterms.dateAccepted2020-11-10
rioxxterms.versionofrecord10.15252/embj.2020105496
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2021-03
dc.contributor.orcidNavarro, Isabela Cunha [0000-0002-6844-2361]
dc.contributor.orcidTuorto, Francesca [0000-0003-1625-1181]
dc.contributor.orcidMiska, Eric A [0000-0002-4450-576X]
dc.identifier.eissn1460-2075
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (104640/Z/14/Z)
pubs.funder-project-idCancer Research UK (A27826)
pubs.funder-project-idWellcome Trust (092096/Z/10/Z)
pubs.funder-project-idWellcome Trust (203144/Z/16/Z)
pubs.funder-project-idCancer Research UK (C6946/A24843)
cam.issuedOnline2020-12-07
cam.orpheus.successMon Dec 14 07:30:51 GMT 2020 - Embargo updated
cam.orpheus.counter7
rioxxterms.freetoread.startdate2021-06-07


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