Widespread occurrence of 5-methylcytosine in human coding and non-coding RNA

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dc.contributor.authorSquires, Jeffrey
dc.contributor.authorPatel, Hardip
dc.contributor.authorNousch, Marco
dc.contributor.authorSibbritt, Tennille
dc.contributor.authorHumphreys, David T
dc.contributor.authorParker, Brian J
dc.contributor.authorSuter, Catherine M
dc.contributor.authorPreiss, Thomas
dc.date.accessioned2015-12-07T22:17:28Z
dc.date.issued2012
dc.date.updated2016-02-24T10:16:51Z
dc.description.abstractThe modified base 5-methylcytosine (m 5C) is well studied in DNA, but investigations of its prevalence in cellular RNA have been largely confined to tRNA and rRNA. In animals, the two m 5C methyltransferases NSUN2 and TRDMT1 are known to modify specific tRNAs and have roles in the control of cell growth and differentiation. To map modified cytosine sites across a human transcriptome, we coupled bisulfite conversion of cellular RNA with next-generation sequencing. We confirmed 21 of the 28 previously known m 5C sites in human tRNAs and identified 234 novel tRNA candidate sites, mostly in anticipated structural positions. Surprisingly, we discovered 10275 sites in mRNAs and other non-coding RNAs. We observed that distribution of modified cytosines between RNA types was not random; within mRNAs they were enriched in the untranslated regions and near Argonaute binding regions. We also identified five new sites modified by NSUN2, broadening its known substrate range to another tRNA, the RPPH1 subunit of RNase P and two mRNAs. Our data demonstrates the widespread presence of modified cytosines throughout coding and non-coding sequences in a transcriptome, suggesting a broader role of this modification in the post-transcriptional control of cellular RNA function.
dc.identifier.issn0305-1048
dc.identifier.urihttp://hdl.handle.net/1885/18580
dc.publisherOxford University Press
dc.rightsAuthor/s retain copyrighten_AU
dc.sourceNucleic Acids Research
dc.subjectKeywords: 5 methylcytosine; argonaute protein; bisulfite; messenger RNA; nsun2 protein; protein methyltransferase; ribonuclease; ribosome RNA; transfer RNA; unclassified drug; untranslated RNA; article; controlled study; enzyme substrate; human; human cell; nucleic
dc.titleWidespread occurrence of 5-methylcytosine in human coding and non-coding RNA
dc.typeJournal article
dcterms.accessRightsOpen Accessen_AU
local.bibliographicCitation.issue11
local.bibliographicCitation.lastpage5033
local.bibliographicCitation.startpage5023
local.contributor.affiliationSquires, Jeffrey, Victor Chang Cardiac Research Institute
local.contributor.affiliationPatel, Hardip, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationNousch, Marco, Victor Chang Cardiac Institute
local.contributor.affiliationSibbritt, Tennille, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationHumphreys, David T, Victor Chang Chardiac Research Institute
local.contributor.affiliationParker, Brian J, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationSuter, Catherine M, Victor Chang Cardiac Research Institute
local.contributor.affiliationPreiss, Thomas, College of Medicine, Biology and Environment, ANU
local.contributor.authoremailu4269546@anu.edu.au
local.contributor.authoruidPatel, Hardip, u4269546
local.contributor.authoruidSibbritt, Tennille, u5074909
local.contributor.authoruidParker, Brian J, u5066093
local.contributor.authoruidPreiss, Thomas, u5046545
local.description.notesImported from ARIES
local.identifier.absfor119999 - Medical and Health Sciences not elsewhere classified
local.identifier.absseo970106 - Expanding Knowledge in the Biological Sciences
local.identifier.ariespublicationu3526593xPUB5
local.identifier.citationvolume40
local.identifier.doi10.1093/nar/gks144
local.identifier.scopusID2-s2.0-84860751168
local.identifier.thomsonID000305032500036
local.identifier.uidSubmittedByu3526593
local.type.statusPublished Version

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