Tracking RNA modifications  to understand early health effects of oxidative-prone air

We are investigating potential chemical modifications that are induced in mRNAs upon exposure to oxidative-prone air and to study how these perturbations affect normal patterns of cellular regulation. Given increasing findings that RNA modifications play a key regulatory role in gene transcription under cellular stress conditions and disease, two fundamental questions are: (1) what biochemical mechanisms lead to the breakdown of normal (healthy) expression levels of these mRNAs in their respective pathways? And, (2) how is the breakdown of biological function at the molecular level caused by environmentally-induced chemical modifications? The major hypothesis we have been investigating in this work is that changes in mRNA expression stem from environmentally induced chemical modifications to mRNAs. As supporting preliminary evidence, we have found that RNAs in BEAS-2B lung epithelial cells undergo significant 8-OG modifications when exposed to levels of ozone and carbonyl mixtures. In this talk, we will discuss our findings uncovering specific mRNAs that are more susceptible to oxidative species and the impact of these modifications on overall cell function. We will also discuss our work understanding the recognition of modified RNAs by protein complexes that are involved in regulating their functions inside cells.