Intracellular ribonucleases in RNA metabolism and disease

Ribonucleases are central components of the eukaryotic RNA processing and decay machineries. They participate in processing of stable RNA species and pre-mRNA molecules as well as remove unwanted molecules like: RNA processing by-products and malformed RNA species that are identified by surveillance pathways. Finally, ribonucleases participle in mRNA turnover and regulated mRNA decay pathways. Interestingly many of such enzymes are connected to various human diseases. Dis3 a catalytic subunit of the primary eukaryotic ribonuclease, the exosome complex, is frequently mutated in Muliple Myeloma. Mutations in the Dis3L2 exonuclease cause Perlmam overgrowth syndrome. Moreover, mutations in the distributive exonuclease USB1 responsible for U6 snRNA 3' end processing causes rare genetic disease Poikiloderma with Neutropenia. This talk will provide an overview on our recent progress in understanding the cellular function of the above mentioned enzymes and in case of Dis3 the application of basic biological knowledge obtained by us to putative therapeutic approaches. FEBS National Lecture