Chemical modifications of proteins, DNA and RNA nucleoside moieties, play critical roles in regulating gene expression. Emerging evidence suggests these RNA modifications (epitranscriptomics) have substantive roles in basic biological processes. Recent studies in yeast, Drosophila and rodent models demonstrate stressors can induce RNA modifications, with specific epitranscriptomic reprogramming of some regulatory RNAs. The NIEHS seeks to solicit innovative, mechanistic research applications that are focused on how environmental exposures are associated and involved with the functional activities of RNA modifications and pathways that may be modified or misregulated, associated with adverse health outcomes, and/or be useful as biomarkers of exposure and/or exposure-induced pathologies. The NIEHS will use the R01 mechanism to support hypothesis driven research using approaches that incorporate principles of toxicology with RNA modification biological and/or chemical expertise and utilizes state of the art technologies.