PROJECT SUMMARY All life forms must maintain a homeostatic gene expression program, which is achieved at many different steps in gene expression, including by the degradation of specific mRNAs and non-coding RNAs. Many evolutionarily conserved RNA processing enzymes mediate these key post-transcriptional events, with important roles for endo and exoribonucleases. A number of inherited diseases are caused by mutations in endo- or exoribonuclease genes, further underscoring their importance for human health. Eukaryotes use exonucleases for the degradation of most cellular mRNAs and for the 5' and 3' end processing of many different ncRNAs. In addition, endonucleases target specific mRNAs as an initiating step in mRNA degradation and other endonucleases process ncRNAs. This proposal will focus on the functional characterization of ribonucleases, especially functions in cytoplasmic mRNA degradation.