Epitranscriptomic alterations induced by environmental toxins: implications for RNA modifications and disease

Genes and Environment, vol. 47, pp. 14

Abstract

Epitranscriptomics, the study of chemical modifications on RNA molecules, has emerged as a vital regulatory layer in gene expression. Among the numerous RNA modifications, N6-methyladenosine (m6A), 5-methylcytosine (m5C), and pseudouridine (Ψ) are particularly significant in maintaining RNA stability, splicing, translation, and cellular function. This review specifically explores how environmental toxins such as heavy metals, air pollutants, pesticides, and endocrine-disrupting chemicals can disrupt RNA modifications, leading to pathophysiological consequences. By focusing on major RNA marks and their associated regulatory enzymes (writers, erasers, and readers), we elucidate the molecular mechanisms through which toxins impair RNA processing and translation. These disruptions have been increasingly linked to disease development, including cancer, neurodegenerative disorders, metabolic syndromes, and immune dysfunction. Moreover, the review highlights recent technological advances such as high-throughput sequencing, mass spectrometry, and CRISPR-based RNA editing that enable detection and characterization of epitranscriptomic changes. Importantly, RNA modifications are dynamic and reversible, making them promising candidates for use as early biomarkers of environmental exposure and disease risk. We also discuss emerging non-canonical RNA modifications and their roles in toxicological responses. The potential of RNA-based biomarkers to enhance environmental health monitoring and precision medicine is significant, although challenges such as methodological standardization, context-specific variability, and clinical translation remain. This synthesis offers a focused, mechanistic perspective on the intersection of RNA biology and environmental toxicology, emphasizing the relevance of RNA modifications as both molecular targets and diagnostic tools in assessing the biological impact of environmental insults.

Authors 6

1. Esther Ugo Alum corresponding

   Kampala International University

   Affiliation as printed

   Department of Research and Publications, Kampala International University, P. O. Box 20000, Kampala, Uganda. alumesther79@gmail.com

2. Regina Idu Ejemot-Nwadiaro

   Kampala International University

   Affiliation as printed

   Directorate of Research, Innovation, Consultancy and Extension (RICE), Kampala International University, Kampala, Uganda

3. Mariam Basajja Aachen Leiden Institute of Advanced Computer Science

   Leiden University

   Affiliation as printed

   Leiden Institute of Advanced Computer Science (LIACS), Leiden University, Leiden, Netherlands

4. Daniel Ejim Uti

   Kampala International University · Federal University of Health Sciences, Otukpo

   Affiliation as printed

   Department of Biochemistry, Faculty of Basic Medical Sciences, Federal University of Health Sciences, Otukpo, Benue State, Nigeria

   Department of Research and Publications, Kampala International University, P. O. Box 20000, Kampala, Uganda

5. Okechukwu Paul-Chima Ugwu

   Kampala International University

   Affiliation as printed

   Department of Research and Publications, Kampala International University, P. O. Box 20000, Kampala, Uganda

6. Patrick Maduabuchi Aja

   Kampala International University

   Affiliation as printed

   Department of Biochemistry, Kampala International University, P. O. Box 20000, Kampala, Uganda