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

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Villaseñor-Altamirano , A B , Watson , J D , Prokopec , S D , Yao , C Q , Boutros , P C , Pohjanvirta , R , Valdés-Flores , J & Elizondo , G 2019 , ' 2,3,7,8-Tetrachlorodibenzo-p-dioxin modifies alternative splicing in mouse liver ' , PLoS One , vol. 14 , no. 8 , 0219747 . https://doi.org/10.1371/journal.pone.0219747

Title: 2,3,7,8-Tetrachlorodibenzo-p-dioxin modifies alternative splicing in mouse liver
Author: Villaseñor-Altamirano, Ana B.; Watson, John D.; Prokopec, Stephenie D.; Yao, Cindy Q.; Boutros, Paul C.; Pohjanvirta, Raimo; Valdés-Flores, Jesús; Elizondo, Guillermo
Contributor organization: Food Hygiene and Environmental Health
Helsinki One Health (HOH)
Raimo Pohjanvirta / Principal Investigator
Date: 2019-08-06
Language: eng
Number of pages: 18
Belongs to series: PLoS One
ISSN: 1932-6203
DOI: https://doi.org/10.1371/journal.pone.0219747
URI: http://hdl.handle.net/10138/307525
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 significantly altered after TCDD treatment. These findings show that the exposure to TCDD has an impact on alternative-splicing, and suggest a new avenue for understanding TCDD-mediated toxicity and pathogenesis.
1182 Biochemistry, cell and molecular biology
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion

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