Functional RNA Modifications Environment and Disease (FRAMED) (R01 Clinical Trial Not Allowed)

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Chemical modifications of protein, DNA and RNA nucleoside moieties play critical roles in regulating gene expression. Emerging evidence suggests RNA modifications have substantive roles in multiple basic biological processes. Epitranscriptomics can be defined as the aggregate suite of functional biochemical modifications to the transcriptome within a cell. Recent studies in yeast, Drosophila, rodent and human models demonstrate that stressors can induce RNA modifications, with specific 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 study of functional chemical RNA modification has identified important emerging roles in cellular regulation and gene expression. However, the impact of environmental exposures on functional RNA modifications has been relatively understudied and may present a new mechanism for enhanced understanding the relationships between exposures and the development of complex human diseases. 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.

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