Control of Pre-mRNA Metabolism in Drosophila

University Of North Carolina At Chapel Hill, Chapel Hill NC

Investigators

Abstract

This project is an investigation of the function of Suppressor of sable, [Su(s)], a novel protein that negatively regulates gene expression in Drosophila. Prior studies have established that this nuclear RNA binding protein represses the production/accumulation of aberrant mRNA from transposon insertion mutant alleles of a variety of genes. In addition, Su(s) has been shown to fine-tune the expression of certain developmentally-regulated wild-type genes. A null su(s) mutant exhibits reduced viability and cold-sensitive male sterility and is hypersensitive to several forms of environmental stress. It has been unclear which step in gene expression is controlled by Su(s), although mounting evidence indicates that this protein either regulates transcription or a co-transcriptional process. This project outlines three main objectives. The first objective is to test the hypothesis that Su(s) regulates transcription of heat-shock inducible genes through nuclear run-on and chromatin immunoprecipitation analysis. The second objective is to map the cis-sequences that mediate the binding and activity of Su(s). This will involve generating and analyzing a set of heat-shock inducible lacZ reporter transgenes. The third objective is to identify proteins that interact with Su(s) by using an epitope-tagging/ mass spectroscopy approach. The intellectual merit of this project lies in its promise for yielding novel insights into genetic control mechanisms that prevent accumulation of aberrant mRNA and promote efficient cellular responses to developmental and physiological signals. The broader impact of this project is its contribution to the development of human resources in science. This ongoing project has supported the training of numerous graduate and undergraduate students. Furthermore, the PI is actively involved in developing programs to enhance the academic experience of undergraduate science majors and to increase the participation and success of underrepresented groups in scientific research.