THE DEVELOPMENTALLY-REGULATED DROSOPHILA GENE ROX8 ENCODES AN RRM-TYPE RNA-BINDING PROTEIN STRUCTURALLY RELATED TO HUMAN TIA-1-TYPE NUCLEOLYSINS

We report the molecular analysis of a novel Drosophila melanogaster ge ne, rox8, isolated in a PCR-based screen for sequences encoding RRM-ty pe RNA-binding polypeptides. The rox8 gene is predicted to encode a 50 -kilodalton protein displaying extensive amino acid sequence similarit ies (46% overall identity; 57 to 60% similarity) to the two recently d escribed human TIA-1-type nucleolysins. These cytolytic granule associ ated proteins, which bind polyadenylated sequences in vitro and trigge r DNA fragmentation in permeabilized target cells, are suspected to pa rticipate in the apoptotic cell death pathway induced by T-lymphocytes and natural killer cells. The structural relatedness of the three pro teins includes three tandemly-repeated consensus RNA-recognition motif s at the N-terminal end and a putative membrane targeting signal at th e C-terminal end. rox8 cytologically maps to 95D5-9 on the right arm o f the third chromosome. Two rox8 transcripts of 3 and 3.3 kb in length , respectively, result from a developmentally-modulated alternative us age of different polyadenylation sites and are differentially accumula ted throughout out the fly life cycle. Molecular characterization of r ox8 represents the first step in a genetic analysis of the potential r oles of a TIA-1-related protein in RNA metabolism and/or programmed ce ll death in Drosophila.