Elucidating the role of long non-coding RNAs in the innate immune response: Identification of functional domains that regulate inflammation

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Upon completion of the human genome project, the biggest surprise was that humans have far fewer genes than previously expected (~ 19,000) and that this is coded by less than 2% of the available DNA. Significantly, recent studies have suggested that much of the remaining 98% of DNA is turned into 'non-coding RNA' and that these are important regulators of gene expression. For convenience, we commonly divide this non-coding RNA into small non-coding RNAs and long non-coding RNAs. At the present time, we have little idea about the role of the majority of this non-coding RNA although recent studies have indicated that these may regulate the immune response. In order to fight infection by bacteria, fungi and viruses, the body has a complex defense system called the immune response. This involves the recognition of these microorganisms and release of a range of chemicals that recruit and activate immune cells (inflammation) that are involved in removing these un-wanted invaders. Under normal conditions, this inflammatory response is then switched off. However, under certain circumstances, prolonged activation can be life-threatening or lead to the development of common conditions such as asthma, diabetes, cancer and cardiovascular disease. For this reason, it is important to understand the mechanisms that regulate both the activation and inhibition of this immune response. Previous studies have shown that the immune response is controlled by a family of small non-coding RNAs called microRNAs. Significantly, we have preliminary evidence showing that long non-coding RNAs might also be novel regulators of innate immunity, specifically by controlling the release of the chemicals used to kill the invading microorganisms. In this project, we will extend these studies by identifying those long non-coding RNAs that regulate this inflammatory response in both human and mouse cells. Using this information, we will then identify and validate the sequences that are important in mediating their actions. Overall, these investigations will help us understand the role of long non-coding RNAs as regulators of inflammation and the immune response to invading pathogens.