RNA oxidation in chromatin modification and DNA-damage response following exposure to formaldehyde

Abstract Formaldehyde is an environmental and occupational chemical carcinogen implicated in the damage of proteins and nucleic acids. However, whether formaldehyde provokes modifications of RNAs such as 8-oxo-7,8-dihydroguanine (8-oxoG) and the role that these modifications play on conferring long-...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Juan C. Gonzalez-Rivera, Mark W. Sherman, Dongyu S. Wang, Jamie C. L. Chuvalo-Abraham, Lea Hildebrandt Ruiz, Lydia M. Contreras
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2020
Materias:
R
Q
Acceso en línea:https://doaj.org/article/a6b0a7d779c54fffba24d73f343cad82
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:a6b0a7d779c54fffba24d73f343cad82
record_format dspace
spelling oai:doaj.org-article:a6b0a7d779c54fffba24d73f343cad822021-12-02T18:37:06ZRNA oxidation in chromatin modification and DNA-damage response following exposure to formaldehyde10.1038/s41598-020-73376-72045-2322https://doaj.org/article/a6b0a7d779c54fffba24d73f343cad822020-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-73376-7https://doaj.org/toc/2045-2322Abstract Formaldehyde is an environmental and occupational chemical carcinogen implicated in the damage of proteins and nucleic acids. However, whether formaldehyde provokes modifications of RNAs such as 8-oxo-7,8-dihydroguanine (8-oxoG) and the role that these modifications play on conferring long-term adverse health effects remains unexplored. Here, we profile 8-oxoG modifications using RNA-immunoprecipitation and RNA sequencing (8-oxoG RIP-seq) to identify 343 RNA transcripts heavily enriched in oxidations in human bronchial epithelial BEAS-2B cell cultures exposed to 1 ppm formaldehyde for 2 h. RNA oxidation altered expression of many transcripts involved in chromatin modification and p53-mediated DNA-damage responses, two pathways that play key roles in sustaining genome integrity and typically deregulated in tumorigenesis. Given that these observations were identified in normal cells exhibiting minimal cell stress and death phenotypes (for example, lack of nuclear shrinkage, F-actin alterations or increased LDH activity); we hypothesize that oxidative modification of specific RNA transcripts following formaldehyde exposure denotes an early process occurring in carcinogenesis analogous to the oxidative events surfacing at early stages of neurodegenerative diseases. As such, we provide initial investigations of RNA oxidation as a potentially novel mechanism underlying formaldehyde-induced tumorigenesis.Juan C. Gonzalez-RiveraMark W. ShermanDongyu S. WangJamie C. L. Chuvalo-AbrahamLea Hildebrandt RuizLydia M. ContrerasNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-16 (2020)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Juan C. Gonzalez-Rivera
Mark W. Sherman
Dongyu S. Wang
Jamie C. L. Chuvalo-Abraham
Lea Hildebrandt Ruiz
Lydia M. Contreras
RNA oxidation in chromatin modification and DNA-damage response following exposure to formaldehyde
description Abstract Formaldehyde is an environmental and occupational chemical carcinogen implicated in the damage of proteins and nucleic acids. However, whether formaldehyde provokes modifications of RNAs such as 8-oxo-7,8-dihydroguanine (8-oxoG) and the role that these modifications play on conferring long-term adverse health effects remains unexplored. Here, we profile 8-oxoG modifications using RNA-immunoprecipitation and RNA sequencing (8-oxoG RIP-seq) to identify 343 RNA transcripts heavily enriched in oxidations in human bronchial epithelial BEAS-2B cell cultures exposed to 1 ppm formaldehyde for 2 h. RNA oxidation altered expression of many transcripts involved in chromatin modification and p53-mediated DNA-damage responses, two pathways that play key roles in sustaining genome integrity and typically deregulated in tumorigenesis. Given that these observations were identified in normal cells exhibiting minimal cell stress and death phenotypes (for example, lack of nuclear shrinkage, F-actin alterations or increased LDH activity); we hypothesize that oxidative modification of specific RNA transcripts following formaldehyde exposure denotes an early process occurring in carcinogenesis analogous to the oxidative events surfacing at early stages of neurodegenerative diseases. As such, we provide initial investigations of RNA oxidation as a potentially novel mechanism underlying formaldehyde-induced tumorigenesis.
format article
author Juan C. Gonzalez-Rivera
Mark W. Sherman
Dongyu S. Wang
Jamie C. L. Chuvalo-Abraham
Lea Hildebrandt Ruiz
Lydia M. Contreras
author_facet Juan C. Gonzalez-Rivera
Mark W. Sherman
Dongyu S. Wang
Jamie C. L. Chuvalo-Abraham
Lea Hildebrandt Ruiz
Lydia M. Contreras
author_sort Juan C. Gonzalez-Rivera
title RNA oxidation in chromatin modification and DNA-damage response following exposure to formaldehyde
title_short RNA oxidation in chromatin modification and DNA-damage response following exposure to formaldehyde
title_full RNA oxidation in chromatin modification and DNA-damage response following exposure to formaldehyde
title_fullStr RNA oxidation in chromatin modification and DNA-damage response following exposure to formaldehyde
title_full_unstemmed RNA oxidation in chromatin modification and DNA-damage response following exposure to formaldehyde
title_sort rna oxidation in chromatin modification and dna-damage response following exposure to formaldehyde
publisher Nature Portfolio
publishDate 2020
url https://doaj.org/article/a6b0a7d779c54fffba24d73f343cad82
work_keys_str_mv AT juancgonzalezrivera rnaoxidationinchromatinmodificationanddnadamageresponsefollowingexposuretoformaldehyde
AT markwsherman rnaoxidationinchromatinmodificationanddnadamageresponsefollowingexposuretoformaldehyde
AT dongyuswang rnaoxidationinchromatinmodificationanddnadamageresponsefollowingexposuretoformaldehyde
AT jamieclchuvaloabraham rnaoxidationinchromatinmodificationanddnadamageresponsefollowingexposuretoformaldehyde
AT leahildebrandtruiz rnaoxidationinchromatinmodificationanddnadamageresponsefollowingexposuretoformaldehyde
AT lydiamcontreras rnaoxidationinchromatinmodificationanddnadamageresponsefollowingexposuretoformaldehyde
_version_ 1718377818480443392