RNA molecules play critical roles in regulating gene expression. Perturbation of RNA processing and metabolism underlies a wide range of human diseases. RNA research in the Department of Genetics and Genome Sciences includes studies designed to uncover the fundamental mechanistic properties of RNA biogenesis, how RNA controls gene expression in normal development and why defects in this process lead to disease.
In the nucleus, protein-coding genes are transcribed into pre-mRNAs that are processed to generate mRNAs. Alternative pre-mRNA splicing represents an important mechanism in gene expression control. The research group led by Hua Lou studies how alternative splicing is controlled dynamically under physiological conditions, and the biological consequences of disrupted expression of splicing isoforms.
Recent studies also demonstrated that the human genome encodes thousands of genes that produce RNA molecules with no protein-coding capacity (microRNAs, long non-coding RNAs, etc). The group led by Ahmad Khalil focuses on large intervening non-coding RNAs (lincRNAs), investigating the roles of lincRNAs in guiding chromatin remodeling complexes to specific loci to control transcription, and the mechanisms by which lincRNAs function. The lab studies lincRNAs in various human diseases with a major focus on human cancers.
In the cytoplasm, RNA regulation is primarily achieved through modulation of the localization, translation and degradation of mRNA. In addition, RNA quality control pathways exist to identify faulty mRNA and target it to rapid degradation. The group led by Kristian Baker focuses on one of these pathways - the nonsense-mediated mRNA decay (NMD) pathway - and on determining how NMD substrates are recognized and how the RNA is targeted to multiple pathways of degradation. The group led by Maria Hatzoglou is interested in identifying the stress-induced changes in mRNA translation machinery and the translated populations of cellular mRNAs (translatomes) and how this leads to the progression of diseases (diabetes, ocular, cancer).
RNA binding proteins (RBPs) control RNA biogenesis. The group led by Ashleigh Schaffer focuses on identifying novel disease-causing RBP mutations in children with neurological disorders, as well as investigating cellular and pathogenic mechanisms of ubiquitous RBPs in human brain development. The group led by Helen Salz focuses on Sex-lethal (Sxl), an RBP that regulates all aspects of Drosophila female-specific development and behavior, including germ cell development.