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

Cayir, Akin, Barrow, Timothy, Guo, Liqiong and Byun, Hyang-Min (2019) Exposure to environmental toxicants reduces global N6-methyladenosine RNA methylation and alters expression of RNA methylation modulator genes. Environmental Research, 175. pp. 228-234. ISSN 0013-9351

Item Type: Article

Abstract

The epitranscriptome comprises more than 100 forms of RNA modifications. Of these, N6-methyladenosine (m6A) 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 in m6A RNA methylation in A549 lung epithelial cells in response to environmental toxicants, and differential gene expression of m6A 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 m6A 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 m6A methylation level significantly decreased with exposure to >62 μg/ml PM, >1 μM sodium arsenite, >1  μM bisphenol A (BPA), and 0.1  μM vinclozolin. In an analysis of a published dataset derived from a population study, we observed that m6A 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 m6A writer METTL3 shows reduced expression in lung tumors in comparison to normal lung epithelia (p < 0.0001). Our findings reveal that m6A RNA methylation can be modified by exposure to environmental toxicants, and exposure to particulate matter is associated with differential expression level of m6A RNA methylation modification machinery.

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More Information

Depositing User: Timothy Barrow

Identifiers

Item ID: 10860
Identification Number: https://doi.org/10.1016/j.envres.2019.05.011
ISSN: 0013-9351
URI: http://sure.sunderland.ac.uk/id/eprint/10860
Official URL: https://www.sciencedirect.com/science/article/pii/...

Users with ORCIDS

ORCID for Timothy Barrow: ORCID iD orcid.org/0000-0003-4551-3857

Catalogue record

Date Deposited: 13 Jun 2019 10:34
Last Modified: 30 Sep 2020 11:02

Contributors

Author: Timothy Barrow ORCID iD
Author: Akin Cayir
Author: Liqiong Guo
Author: Hyang-Min Byun

University Divisions

Faculty of Health Sciences and Wellbeing

Subjects

Sciences > Biomedical Sciences
Sciences > Environment
Sciences > Health Sciences

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