Phantoms in the Transcriptome: How Nucleic Acid Modifications Shape Gene Expression in Development and Disease

CCR Grand Rounds Research in the Oberdoerffer laboratory examines the role of DNA and RNA modifications in determining: 1) how a single gene generates multiple protein-coding variants and 2) how a single messenger RNA (mRNA) molecule dictates distinct protein fates during the process of translation. As the archetype for epigenetic control within DNA, they specifically examine how nucleic acid modifications of cytosine influence gene expression at unexpected stages in the life cycle of an mRNA. Dr. Oberdoerffer and colleagues investigate 5mC and its oxidized derivatives in genic DNA and ask whether elevated detection at exons relative to introns in DNA reflects a role in co-transcriptional pre-mRNA splicing. In addition, in investigating cytosine modifications in RNA, they found an unexpected prevalence of cytosine acetylation in mRNA (N4-acetylcytidine, ac4C). Investigation of ac4C enzymatic regulation and function revealed a post-transcriptional role in mRNA translation. The overarching theme of the Oberdoerffer laboratory focuses on innovative connections between the epigenome, epitranscriptome and mRNA metabolism. Ultimately, the researchers aim to understand how cytosine modifications contribute to the etiology of disease and potentially identify avenues for novel therapeutic interventions.Air date: 11/1/2019 12:00:00 PM
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