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-...
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Nature Portfolio
2020
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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) |
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Medicine R Science Q |
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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 |