Small RNA Regulation in Drosophila

The surface of the earth is populated by living things with extraordinary different appearances. However, they all made of cells and these units of life share the same set of organelles (‘small organs’) for their most basic functions. These small organs are present in almost every cell in our bodies and if they do not work properly, we will get sick or even die. The Liu group is interested in a few newly-found small organs within the cell and try to study how they work in the fruit fly, one of the most studied living things on our planet. Learning more about how these small organs work in fruit flies will help us to understand how they work in human and to find a better way to cure related disease.

Intracellular compartments such as organelles are essential for a cell’s function. RNA occurs in every compartment in a cell. Research in the Liu group focuses on three fundamental questions relating to RNA, for which we seek an in vivo understanding. We choose the fruitfly Drosophila melanogaster as our prime model system because of its genetic tractability and the depth of genomic data. Studies in Drosophila have provided a key to vertebrate development and human biology. First, we will study the mechanisms by which the synthesis of CTP, one of the critical precursors of RNA and DNA, is compartmentalized within a cell. We have recently discovered that CTP synthase is compartmentalized in a novel evolutionarily conserved organelle, the cytoophidium. Compartmentation is essential for the localization of biological processes within a eukaryotic cell. CTP synthase has been an attractive target for developing agents against cancer, virus and parasites. We will investigate how CTP synthase is assembled into the cytoophidium and how the cytoophidium is linked to cancer biology. Second, we are interested in the biological roles of long noncoding RNAs in Drosophila. While much knowledge has been gained on the functionality of protein-coding genes, we know very little about the mechanisms by which noncoding RNAs function in a fly. We will analyse the spatial and temporal expression of long noncoding RNAs during Drosophila development and will investigate the underlying mechanisms of how they function in vivo. Finally, we will investigate how an RNP assembly and RNA splicing factor SMN and the abundance of U bodies are regulated during development. SMN, a major constituent of U bodies which contain snRNPs, is the determining factor for SMA. The study of SMN and the U body thus holds the key to identifying the cellular mechanism of SMA. We are particularly excited to investigate the role of SMN in the maintenance of stem cells and their pluripotency.