Post-transcriptional air pollution oxidation to the cholesterol biosynthesis pathway promotes pulmonary stress phenotypes.

Communications Biology
Juan C Gonzalez-RiveraLydia M Contreras

Abstract

The impact of environmentally-induced chemical changes in RNA has been fairly unexplored. Air pollution induces oxidative modifications such as 8-oxo-7,8-dihydroguanine (8-oxoG) in RNAs of lung cells, which could be associated with premature lung dysfunction. We develop a method for 8-oxoG profiling using immunocapturing and RNA sequencing. We find 42 oxidized transcripts in bronchial epithelial BEAS-2B cells exposed to two air pollution mixtures that recreate urban atmospheres. We show that the FDFT1 transcript in the cholesterol biosynthesis pathway is susceptible to air pollution-induced oxidation. This process leads to decreased transcript and protein expression of FDFT1, and reduced cholesterol synthesis in cells exposed to air pollution. Knockdown of FDFT1 replicates alterations seen in air pollution exposure such as transformed cell size and suppressed cytoskeleton organization. Our results argue of a possible novel biomarker and of an unseen mechanism by which air pollution selectively modifies key metabolic-related transcripts facilitating cell phenotypes in bronchial dysfunction.

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Citations

Oct 8, 2020·Scientific Reports·Juan C Gonzalez-RiveraLydia M Contreras
Sep 2, 2021·Critical Reviews in Toxicology·Akin Cayir

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Methods Mentioned

BETA
RIP-seq
ELISA
RIP
immunoprecipitation
PCR
electrophoresis
transfection
light scattering
pulldown
pulldowns

Software Mentioned

Wavemetrics
Ensembl
FastQC
FibrilTool
GraphPad Prism
Fiji Image J
ImageJ
CELL
STAR
Zen Pro

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