Grant: Discovery Grants Program - Individual

Small ribonucleic acid (RNA) molecules have many essential and varied intracellular functions that affect the expression of genes in organisms ranging from bacteria to humans. We have only recently become aware of the sheer diversity and number of these molecules in some eukaryotic organisms. It is a remarkable discovery that the majority of the human genome may in fact contain sequences coding for small RNA molecules rather than for proteins. In most organisms, however, we still do not know the identity or the intracellular function of these RNAs. A primary objective of my research program will be to characterize novel RNA molecules and to elucidate their specific cellular activities. We will also be examining the means by which these small RNAs are expressed from the genes that encode them. Small RNAs associate in the cell with protein molecules to form ribonucleoprotein (RNP) complexes. Several of the best-characterized RNP complexes are also some of the most ancient biological structures known and their existence predates the divergence of bacterial and eukaryotic organisms several billion years ago. One such class of eukaryotic RNPs are called the small nucleolar (sno)RNPs. These complexes are found in both eukaryotic and archaeal organisms where they play an important role in the synthesis and function of ribosomes. Recent findings also indicate that these RNPs have other distinct and important cellular functions. Another important goal of my research is to determine the detailed mechanism by which these snoRNP complexes function in the process of ribosome synthesis and assembly. We will also investigate the evolution of these complexes by comparing their structure and function in distantly-related organisms. Towards this goal, I have chosen to examine these complexes in the group of unicellular eukaryotic organisms known as protists. In these studies, we will not only be striving to enhance our understanding of the structure and function of protein-RNA complexes, but also to obtain the knowledge required to manipulate these structures to perform novel and useful functions in organisms such as humans.