Grant: Operating Grant

Ribosomal proteins (RPs) are abundant RNA-binding proteins that normally function in the folding of ribosomal RNA molecules to allow the formation of the ribosome, the molecular machine responsible for protein synthesis. Surprisingly, however, mutations in RP genes can perturb specific cellular processes, which is not expected if RPs function exclusively in the universal process of making ribosomes. Consistent with the view that RP may have specialized cellular roles, mutations in RP genes are the underlying genetic defects of a collection of human disorders known as ribosomopathies, which have distinct clinical phenotypes. The molecular basis whereby mutations in RP genes cause specific clinical syndromes remains unclear, however. We have recently discovered new auxiliary functions of RPs in yeast and human cells. A major goal of the present application is to the characterize mechanisms by which RPs play such regulatory roles as well as identify additional RP specialization events. Elucidation of molecular mechanisms whereby selective abnormalities in RPs cause specific biological defects and/or phenotypes will hopefully lead to novel therapeutic strategies for these diseases.