Exposure to environmental toxicants reduces global N6-methyladenosine RNA methylation and alters expression of RNA methylation modulator genes

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dc.authoridByun, Hyang-Min/0000-0002-6278-3165
dc.authoridguo, liqiong/0000-0002-1141-9646
dc.authoridCAYIR, AKIN/0000-0002-2014-6635
dc.authoridBarrow, Timothy/0000-0003-4551-3857
dc.contributor.authorCayir, Akin
dc.contributor.authorBarrow, Timothy M.
dc.contributor.authorGuo, Liqiong
dc.contributor.authorByun, Hyang-Min
dc.date.accessioned2025-01-27T20:29:00Z
dc.date.available2025-01-27T20:29:00Z
dc.date.issued2019
dc.departmentÇanakkale Onsekiz Mart Üniversitesi
dc.description.abstractThe epitranscriptome comprises more than 100 forms of RNA modifications. Of these, N6-methyladenosine (m(6)A) is the most abundant form of RNA methylation, with roles in modulating mRNA transcript processing and regulation. The aims of the study were to examine changes inm(6)A RNA methylation in A549 lung epithelial cells in response to environmental toxicants, and differential gene expression of m(6)A modulator genes ('readers', 'writers' and 'erasers') in human subjects exposed to particulate matter (PM) and in lung cancer tissue using publicly-available microarray datasets. Global m(6)A methylation levels were measured in total RNA after exposure to two carcinogens (PM and sodium arsenite) for 24- and 48-h, and to two endocrine disruptors (bisphenol A and vinclozolin)for 24-h. Global m(6)A methylation level significantly decreased with exposure to > 62 mu g/mlPM, > 1 mu M sodium arsenite, > 1 mu M bisphenol A (BPA), and 0.1 mu M vinclozolin. In an analysis of a published dataset derived from a population study, we observed that m(6)A writers (METTL3 and WTAP), erasers (FTO and ALKBH5) and readers (HNRPC) showed significantly higher expression among participants in the high-PM2.5 exposure group compared to those in the low-exposure control group (all p < 0.05). Further, the m(6)A writer METTL3 shows reduced expression in lung tumors in comparison to normal lung epithelia (p < 0.0001). Our findings reveal that m(6)A RNA methylation can be modified by exposure to environmental toxicants, and exposure to particulate matter is associated with differential expression level of m(6)A RNA methylation modification machinery.
dc.description.sponsorshipScientific and Technological Research Council of Turkey [TUBITAK-1152684]; Canakkale Onsekiz Mart University BAP [FHD-2017-1087]
dc.description.sponsorshipPublicly available gene expression datasets were obtained from The Cancer Genome Atlas (TCGA) project established by the NIH and National Human Genome Research Institute. This study was supported by The Scientific and Technological Research Council of Turkey (TUBITAK-1152684) and by Canakkale Onsekiz Mart University BAP (FHD-2017-1087).
dc.identifier.doi10.1016/j.envres.2019.05.011
dc.identifier.endpage234
dc.identifier.issn0013-9351
dc.identifier.issn1096-0953
dc.identifier.pmid31146095
dc.identifier.scopus2-s2.0-85066099780
dc.identifier.scopusqualityQ1
dc.identifier.startpage228
dc.identifier.urihttps://doi.org/10.1016/j.envres.2019.05.011
dc.identifier.urihttps://hdl.handle.net/20.500.12428/22768
dc.identifier.volume175
dc.identifier.wosWOS:000473836300024
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherAcademic Press Inc Elsevier Science
dc.relation.ispartofEnvironmental Research
dc.relation.publicationcategoryinfo:eu-repo/semantics/openAccess
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WoS_20250125
dc.subjectRNA methylation
dc.subjectm(6)A
dc.subjectParticulate matter
dc.subjectEnvironmental exposure
dc.titleExposure to environmental toxicants reduces global N6-methyladenosine RNA methylation and alters expression of RNA methylation modulator genes
dc.typeArticle

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