(635f) Epitranscriptomic Regulation Changes in Human Lung Cells in Response to Environmental Stresses.

Exposure to air pollution is linked to diseases of the lungs, brain, and heart and is estimated to contribute to over 7 million deaths annually by the World Health Organization. Although the link between exposure and adverse health effects has been made apparent through epidemiological studies, the role of unique air pollution components in disease pathogenesis needs to be further characterized on the cellular and molecular level. It has recently become apparent that RNA modifications, or the epitranscriptome, have important regulatory roles in many cellular functions, including stress responses. In this study, we conduct quantitative transcriptomics and epitranscriptomics to better understand the effects of environmental toxins on human lung cells.

Specifically, we examine human bronchial epithelial cells (BEAS-2B cells) as a model system to determine the effects of airborne particulate matter (PM) mixtures. We use an interdisciplinary approach involving traditional RNA sequencing and large-scale epitranscriptomics by mass spectrometry, coupled with targeted sequencing techniques to map specific RNA modifications across the transcriptome. Using these systems and quantitative biology tools, we have developed an integrated approach that combines large-scale biological data to understand the interplay between environmentally-induced transcriptional changes and the resulting changes to the epitranscriptome. Collectively, these methods have allowed us to show broad changes in the levels of more than 10 RNA modifications (including m6A, pseudouridine, m5C, among others) can be induced by particulate matter stress. We have also used this approach to show that the epitranscriptome provides an additional method of regulation used to respond to environmental stress by altering patterns of RNA modifications on key RNA transcripts involved in the stress response. Together, this systematic approach helps to deconvolute how the epitranscriptomic regulation contributes to lung cell health. We believe this approach can be broadly applicable to investigate subtle changes in cellular responses to different stimuli and pathologies.