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m<sup>6</sup>A RNA methylation regulatory gene expression in response to ethanol and acetaldehyde exposure and withdrawal.

Overview

Authors: Ji Sun Koo1,2, Qiansheng Zhan1,2, Huiping Zhang1,2
  1. Department of Psychiatry, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, United States
  2. The Biomedical Genetics Section, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, United States
Institutions: Boston University (United States)
Journal: Environmental epigenetics, volume 12, issue 1, article dvag011
Dates: received 23 September 2025; accepted 19 March 2026; published online 26 March 2026
Type: Research article · Language: English
License: CC BY-NC
Identifiers: DOI 10.1093/eep/dvag011 · PMID 41970606 · PMCID PMC13069560 · OpenAlex W7140521421
Open access: diamond, a free copy (OpenAlex)
Categories: genetics / omics (modality), other (modality), histology / microscopy (modality), human (organism), cellular / molecular (subfield)
Methods: Statistics
Keywords: m6A writers, m6A erasers, m6A readers, ethanol/acetaldehyde exposure/withdrawal, RT-qPCR, cellular model, human postmortem brains, RNA-seq
Topic: RNA modifications and cancer (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Citations: not cited yet (Europe PMC); 32 references in the paper

Abstract

6-methyladenosine (m6A) RNA methylation, regulated by writer, eraser, and reader proteins, modulates mRNA stability, splicing, and translation, thereby influencing key cellular processes. Environmental stressors, such as alcohol, may disrupt this epitranscriptomic machinery and contribute to disease vulnerability. In this study, we investigated how chronic exposure to ethanol, its toxic metabolite acetaldehyde, and subsequent withdrawal affect the expression of m6A regulatory genes. Neuron-like (SH-SY5Y) and non-neuronal (SW620) cells were exposed for 3 weeks to ethanol (40 mM) or acetaldehyde (30 μM) (concentrations comparable to blood levels after heavy drinking), followed by a 24-h withdrawal period. Gene expression of seven writers (KIAA1429, METTL3, METTL4, METTL14, RBM15, RBM15B, and WTAP), two erasers (ALKBH5, FTO), and nine readers (YTHDF1/2/3, YTHDC1/2, IGF2BP1/2/3, and HNRNPA2B1) was quantified by RT-qPCR. Concurrently, RNA-seq data from eight reward-related brain regions of 24 individuals of European ancestry (12 with alcohol use disorder [AUD] and 12 controls) were analyzed for AUD-associated expression changes in m6A regulatory genes. In cell models, ethanol broadly suppressed the expression of most m6A regulatory genes, whereas withdrawal largely restored their levels. Acetaldehyde induced subtler gene expression changes, likely reflecting its lower exposure concentration and rapid metabolism. Postmortem brain analysis revealed trends toward altered expression of m6A regulatory genes across multiple brain regions in individuals with AUD. Collectively, these findings suggest that chronic alcohol exposure dysregulates m6A regulatory gene expression and may impact downstream RNA regulatory pathways involved in AUD pathophysiology. Further studies are warranted to elucidate the mechanisms by which alcohol-induced dysregulation of m6A regulators influences AUD risk.

Reproduced under the paper's license (CC BY-NC), from the paper cited above.

Code

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Data

Datasets cited

Data availability

The relative expression levels of m6A regulatory genes are displayed in Supplementary Table 2a–j. The RNA-seq FASTQ files for 192 human postmortem brain tissue samples are publicly available in the NCBI Gene Expression Omnibus (GEO) under accession number GSE181982 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE181982).

Reproduced under the paper's license (CC BY-NC), from the paper cited above.

Versions

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Version 1, 30 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 3 authors, 8 keywords, 1 funder, 31 references.

Cite

This paper

Koo, J. S., Zhan, Q., & Zhang, H. (2026). m<sup>6</sup>A RNA methylation regulatory gene expression in response to ethanol and acetaldehyde exposure and withdrawal. Environmental epigenetics, 12(1), dvag011. https://doi.org/10.1093/eep/dvag011

BibTeX

@article{koo2026m,
author = {Koo, Ji Sun and Zhan, Qiansheng and Zhang, Huiping},
title = {{m\<sup\>6\</sup\>A RNA methylation regulatory gene expression in response to ethanol and acetaldehyde exposure and withdrawal}},
journal = {Environmental epigenetics},
year = {2026},
month = mar,
volume = {12},
number = {1},
pages = {dvag011},
publisher = {Oxford University Press},
issn = {2058-5888},
doi = {10.1093/eep/dvag011},
url = {https://doi.org/10.1093/eep/dvag011},
pmid = {41970606},
pmcid = {PMC13069560}
}

RIS

TY - JOUR
AU - Koo, Ji Sun
AU - Zhan, Qiansheng
AU - Zhang, Huiping
TI - m<sup>6</sup>A RNA methylation regulatory gene expression in response to ethanol and acetaldehyde exposure and withdrawal
T2 - Environmental epigenetics
J2 - Environ Epigenet
PY - 2026
DA - 2026/03/26
VL - 12
IS - 1
SP - dvag011
SN - 2058-5888
PB - Oxford University Press
DO - 10.1093/eep/dvag011
UR - https://doi.org/10.1093/eep/dvag011
LA - en
ER -

CSL-JSON

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