Drosophila RNase H1 is essential for development but not for proliferation

Ribonucleases H (RNases H) recognize and specifically degrade RNA that is bound to complementary DNA and are thought to be involved in DNA replication and transcriptional regulation. Though it was previously shown that bacterial RNases H participate in DNA synthesis, none of the known mutations in RNase H genes in either prokaryotes or lower eukaryotes is lethal. Here, we report the characterization of the first loss-of-function mutation in an RNase Hl gene in a metazoan organism, Drosophila melanogaster. Genetic studies of this mutant showed that this gene is essential for metamorphosis in Drosophila. However, disruption of the RNase HI gene does not affect proliferation, but probably alters the regulation of gene expression. The lethal phenotype of this mutant also demonstrates that RNase HI activity in Drosophila cannot be provided by other cellular RNase H activities. Analysis of the developmental and spatial expression profiles of a reporter gene placed under the control of the RNase HI promoter revealed increased expression in several larval tissues. In salivary glands this increase was shown to be inducible by treatment with ecdysone.