2,3,7,8-Tetrachlorodibenzo-p-dioxin modifies alternative splicing in mouse liver

PloS One
Ana B Villaseñor-AltamiranoGuillermo Elizondo

Abstract

Alternative splicing is a co-transcriptional mechanism that generates protein diversity by including or excluding exons in different combinations, thereby expanding the diversity of protein isoforms of a single gene. Abnormalities in this process can result in deleterious effects to human health, and several xenobiotics are known to interfere with splicing regulation through multiple mechanisms. These changes could lead to human diseases such as cancer, neurological disorders, autoimmune diseases, and developmental disorders. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant generated as a byproduct of various industrial activities. Exposure to this dioxin has been linked to a wide range of pathologies through the alteration of multiple cellular processes. However, the effects of TCDD exposure on alternative splicing have not yet been studied. Here, we investigated whether a single po. dose of 5 μg/kg or 500 μg/kg TCDD influence hepatic alternative splicing in adult male C57BL/6Kou mouse. We identified several genes whose alternative splicing of precursor messenger RNAs was modified following TCDD exposure. In particular, we demonstrated that alternative splicing of Cyp1a1, Ahrr, and Actn1 was significa...Continue Reading

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Citations

Jan 26, 2020·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Andrew J AnnaloraPatrick L Iversen
Oct 17, 2020·Toxicological Sciences : an Official Journal of the Society of Toxicology·Neelakanteswar Aluru, Sibel I Karchner

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Methods Mentioned

BETA
PCR
chips

Software Mentioned

ARH package
limma
latticeExtra
Bioconductor
Ensembl
moex10sttranscriptcluster
lattice
oligo
R
Dotmap

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