Discovery of functional genes in the post-genome era by novel RNA-protein hybrid ribozymes

Novel ribozymes were constructed that couple the site specific cleavage activity of the hammerhead ribozyme with the unwinding activity of the endogenous RNA helicase. This leads to extremely efficient cleavage of any target mRNA regardless of the secondary structure of the RNA. Since the novel hybrid ribozymes can attack any site within mRNA, libraries were made of the hybrid ribozymes with randomized binding arms and introduced into cells. This procedure made it possible to readily identify the relevant genes associated with phenotype in the apoptosis pathway. This application of a randomized library of hybrid ribozymes represents a simple powerful method for identification of genes associated with specific phenotypes.