Finding Cis-Regulatory Regions in Long Noncoding RNA Loci

Abstract

We currently understand very little about how the genome functions. Up to 80% of the genome is transcribed, but much of biology focuses on the ~1-5% that codes for proteins. This narrow focus leaves many newly cataloged noncoding transcripts wholly uncharacterized. For the noncoding transcripts that have been studied using cellular and molecular biology techniques, only a handful of animal models have been generated. My PhD work centers on studying the physiological relevance of a set of long intergenic noncoding RNAs (lincRNAs) implicated in development or disease. Specifically, my studies focus on demonstrating how these lincRNA loci affect gene regulation in their local gene neighborhoods (in cis). The first step in this quest is to disentangle whether the RNA transcript or the noncoding DNA within the lincRNA locus is responsible for genetic regulation. I have found that at least six of the thirteen lincRNA loci we examined may function in cis, and have demonstrated that at least two of these loci contain DNA-based enhancers that can explain the functionality of the locus. Collectively, these data provide a foundation from which to address the questions of how noncoding loci influence expression in their local gene neighborhoods, and which molecular species (DNA or RNA) is/are responsible for affecting that function.