The overall goal of this research is to elucidate mechanisms that regulate genetic expression at the levels of transcription, RNA processing, RNA turnover and translation. Attention is focused on the mouse genes encoding ribosomal structural proteins (rp's) and immunoglobulins (ig's). For the rp genes, we are (i) analyzing their distinctive equipotent promoters, (ii) studying the importance of introns for stabilization and intracellular transport of mRNA, and (iii) studying the translational control of rp mRNA. Future studies of these genes will include a characterization of rp transcription factors and the genes encoding them, elucidation of the roles of the oligopyrimidine cap sequence and the internal promoter elements, studies of the interactions between the various promoter elements, an analysis of the intranuclear turnover of intronless transcripts, and definition of the structural features that limit the capacity of rp mRNAs to bind ribosomes. For the ig genes, we are (i) studying the regulation of heavy chain mRNA production by alternative RNA processing, (ii) characterzing the interplay between elements of kappa gene promoters, and (iii) defining the role of the kappa enhancer and chromatin restructuring in the developmental regulation of kappa gene expression. Future studies of these genes will include a comparison of overall cleavage-polyadenylation and splicing efficiencies in early and late stage lymphocytes, a search for the parameters that determine the relative efficiencies of JH-Cmu and JH-Cdelta splicing, characterization of a novel kappa promoter element and its protein ligand, cloning of the gene encoding this ligand, and localization of the genetic segment that confers enchancer-independent expression of the kappa gene. The results of these studies should not only increase knowledge of how rp and ig genes work, but should also reveal general principles that apply to other genes with similar properties. The experiments performed will continue to follow the processes needed to get a gene expressed as a functional protein. These processes are fundamental for most organisms. The results will aid in our understanding of gene expression and be applicable to a wide range of biological problems.
