Epigenetics of RNA: a systems approach

Type of Award: Catalyst
Date Awarded: July 2006
Award End Date: December 2008
Amount Awarded: $ 200,000.00
PI(s): Alfonso Mondragon, PhD, NU; Tao Pan, PhD, UChicago;

Abstract: While the genome sequence encodes the master plan of how an organism works, adapts, and evolves, epigenetics deals with how this master plan is put into practice through chemical modifications of DNA, protein, and RNA. The epigenetic modifications of DNA selectively regulate gene expression. Epigenetic modifications of proteins are crucial for signal transduction and protein activity regulation.

RNA is also epigenetically modified, although this process is not as well studied or understood. Over 100 types of chemical modifications have been identified in thousands of sites in RNA from bacteria to man. However, only a few RNA modifications are essential for life. Instead, many RNA modifications are involved in stress responses and environmental adaptation. An important aspect of RNA modifications is that they may be functionally analogous to protein modifications since many of these modifications are chemically reversible. Reversible modifications would allow sophisticated regulation of the structure and function of modified RNAs.

Our work is concerned with the development of high-throughput methods to study the molecular and mechanistic details of RNA modification enzymes and to study the function of RNA modifications at the genomic level during cell growth and adaptation. Our combination of structural, biochemical and biological approaches should provide a new and unique view of the systems biology of RNA epigenetics.