Molecular mechanisms that control gene function and cell behavior are central to our understanding of and exerting influence on how biological systems integrate system- wide information for growth, development and adaptation. In contrast to DNA and protein, the epigenetics of RNA is a much less explored area. We propose that post- transcriptional RNA modifications could be functionally analogous to post-translational protein modifications. The extent of RNA modifications could depend on the physiological state of the cell. The simultaneous presence of distinctly modified RNA species, all derived from the same gene, would greatly increase the number of functional RNAs that can perform subtle or even significantly different tasks. RNA modification may represent a fundamental source of epigenetic diversity in biological regulation. We aim to discover whether post-transcriptional modifications in biological RNAs are reversible in the cell, to identify the biological RNA targets and the enzymes that catalyze the reversal reactions. We will develop new, high throughput methods to address these questions in /E. coli/ and in human cells. PUBLIC HEALTH RELEVANCE: Epigenetics controls gene expression through chemical modifications of DNA, RNA and proteins. We aim to discover the importance of epigenetics of RNA, in order to fully understand how human cells respond and adapt to varying physiological conditions.

R01GM088599

2009-08-01

2014-07-31