Schistosome Satellite DNA Encodes Active Hammerhead Ribozymes

ABSTRACT

Using a computer program designed to search for RNA structural motifs in sequence databases, we have found a hammerhead ribozyme domain encoded in the Smα 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 bothcis 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 Smα 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 orHeterobilharzia americana, suggesting that the hammerhead domain was not acquired from a common schistosome ancestor.

ACKNOWLEDGMENTS

We thank Véronique Bourdeau, who made the RNAMOT searches, and the members of the sequencing unit of the Organelle Megasequencing Program (OGMP), especially Y. Zhu; Gary O’Neal of Merck Sharpe for providing DNA from S. mansoni; and Scott Snyder for providing specimens of Schistosomatium douthittiand H. americana.

R. Cedergren is Richard Ivey Fellow of the Canadian Institute of Advanced Research. This work was supported by a grant from the Medical Research Council of Canada.