Using a computer program designed to search for RNA structural motifs in sequence databases, we have found a hammerhead ribozyme domain encoded in the Sm␣ repetitive DNA of Schistosoma mansoni. Transcripts of these repeats are expressed as long multimeric precursor RNAs that cleave in vitro and in vivo into unit-length fragments. This RNA domain is able to engage in both cis and trans cleavage typical of the hammerhead ribozyme. Further computer analysis of S. mansoni DNA identified a potential trans cleavage site in the gene coding for a synaptobrevin-like protein, and RNA transcribed from this gene was efficiently cleaved by the Sm␣ ribozyme in vitro. Similar families of repeats containing the hammerhead domain were found in the closely related Schistosoma haematobium and Schistosomatium douthitti species but were not present in Schistosoma japonicum or Heterobilharzia americana, suggesting that the hammerhead domain was not acquired from a common schistosome ancestor.Schistosomes are a family of digenetic trematodes that parasitize many animal species; three members of this group, Schistosoma mansoni, Schistosoma haematobium, and Schistosoma japonicum, infect over 200 million people worldwide. These blood flukes possess a complex life cycle initiated by the release of eggs from a human host. Fluke eggs produce larvae, called miracidia, which infect snails, a secondary host. Snails in turn shed cercariae, another larval form, which are able to penetrate human skin, transform into schistosomula, and, after a complex migration and differentiation process, develop into sexual adults. Adults produce eggs to complete the cycle. Hopefully, the study of the genomic structure of these species could provide key information for the more effective control of these devastating parasites.Most eukaryotic genomes contain families of interspersed repetitive DNA called SINEs (37), the sequences of which are generally related to tRNAs or 7SL RNA (1,3,10,41). Their repetitive nature is thought to be due to an amplification process involving reverse transcription of RNA transcripts which are subsequently integrated into host DNA (21, 40). The species S. mansoni contains a family of SINEs, the 335-bp Sm␣ repeats, which occur over 10,000 times in the haploid genome. Many copies of this repeat are clustered on the W female chromosome, while others are dispersed throughout the genome (38). In spite of this ability to amplify themselves, no function has been ascribed to SINEs.Transcripts of the highly conserved family of satellite DNAs (Sat2) found in the newt do, however, possess a self-processing activity typical of the hammerhead domain found in plant viroids and their satellite RNAs (5,7,13,39). Tandem arrays of the Sat2 repeats are dispersed throughout the genome of Notophthalmus viridescens and other newt species. Their transcripts have tissue-specific 5Ј ends, suggesting that transcription and/or self-cleavage are regulated in vivo (14). Although suggestive, no cellular role has yet been assigned to these self-cleaving transcri...