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

Ana B. Villaseñor-Altamirano, John D. Watson, Stephenie D. Prokopec, Cindy Q. Yao, Paul C. Boutros, Raimo Pohjanvirta, Jesús Valdés-Flores, Guillermo Elizondo

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

Sammanfattning

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.
Originalspråkengelska
TidskriftPLoS One
Volym14
Utgåva8
Sidor (från-till)e0219747
ISSN1932-6203
DOI
StatusPublicerad - 6 aug 2019
MoE-publikationstypA1 Tidskriftsartikel-refererad

Vetenskapsgrenar

  • 1182 Biokemi, cell- och molekylärbiologi

Citera det här

Villaseñor-Altamirano, A. B., Watson, J. D., Prokopec, S. D., Yao, C. Q., Boutros, P. C., Pohjanvirta, R., ... Elizondo, G. (2019). 2,3,7,8-Tetrachlorodibenzo-p-dioxin modifies alternative splicing in mouse liver. PLoS One, 14(8), e0219747. https://doi.org/10.1371/journal.pone.0219747
Villaseñor-Altamirano, Ana B. ; Watson, John D. ; Prokopec, Stephenie D. ; Yao, Cindy Q. ; Boutros, Paul C. ; Pohjanvirta, Raimo ; Valdés-Flores, Jesús ; Elizondo, Guillermo. / 2,3,7,8-Tetrachlorodibenzo-p-dioxin modifies alternative splicing in mouse liver. I: PLoS One. 2019 ; Vol. 14, Nr. 8. s. e0219747.
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title = "2,3,7,8-Tetrachlorodibenzo-p-dioxin modifies alternative splicing in mouse liver",
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.",
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Villaseñor-Altamirano, AB, Watson, JD, Prokopec, SD, Yao, CQ, Boutros, PC, 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, nr. 8, s. e0219747. https://doi.org/10.1371/journal.pone.0219747

2,3,7,8-Tetrachlorodibenzo-p-dioxin modifies alternative splicing in mouse liver. / Villaseñor-Altamirano, Ana B.; Watson, John D.; Prokopec, Stephenie D.; Yao, Cindy Q.; Boutros, Paul C.; Pohjanvirta, Raimo; Valdés-Flores, Jesús; Elizondo, Guillermo.

I: PLoS One, Vol. 14, Nr. 8, 06.08.2019, s. e0219747.

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

TY - JOUR

T1 - 2,3,7,8-Tetrachlorodibenzo-p-dioxin modifies alternative splicing in mouse liver

AU - Villaseñor-Altamirano, Ana B.

AU - Watson, John D.

AU - Prokopec, Stephenie D.

AU - Yao, Cindy Q.

AU - Boutros, Paul C.

AU - Pohjanvirta, Raimo

AU - Valdés-Flores, Jesús

AU - Elizondo, Guillermo

PY - 2019/8/6

Y1 - 2019/8/6

N2 - 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.

AB - 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.

KW - 1182 Biochemistry, cell and molecular biology

U2 - 10.1371/journal.pone.0219747

DO - 10.1371/journal.pone.0219747

M3 - Article

VL - 14

SP - e0219747

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 8

ER -

Villaseñor-Altamirano AB, Watson JD, Prokopec SD, Yao CQ, Boutros PC, Pohjanvirta R et al. 2,3,7,8-Tetrachlorodibenzo-p-dioxin modifies alternative splicing in mouse liver. PLoS One. 2019 aug 6;14(8):e0219747. https://doi.org/10.1371/journal.pone.0219747