The nuclear cap binding complex (CBC) , a heterodimer comprised of CBP20 and CBP90, binds the N7-methylguanosine cap structure that is present on all RNA polymerase II transcripts. It plays critical roles in the methylguanosine cap structure that is present on all RNA polymerase II transcripts. It plays critical roles in the splicing and 3' polyadenylation of precursor mRNA, and in the export of U snRNAs. The CBC is subject to regulation by growth factors, stress, and activated versions of the GTP- binding proteins Ras and Cdc42; thus it provides a link between growth factor-coupled signaling and the control of gene expression at the level of RNA processing. We propose to study biochemical properties and biological functions of the CBC in two general lines of investigation. To understand structure-function relationships in the CBC in molecular detail, we will identify residues of CBP20 that mediate cap binding and heterodimerization. We will determine whether the CBC plays a role in the control of growth and differentiation by manipulating its expression level in NIH/3T3 fibroblasts and then assaying various facets of cell growth and transformation.
