Ribonucleases H (RNases H) recognize and specifically degrade RNA that is b
ound to complementary DNA and are thought to be involved in DNA replication
and transcriptional regulation. Though it was previously shown that bacter
ial RNases H participate in DNA synthesis, none of the known mutations in R
Nase H genes in either prokaryotes or lower eukaryotes is lethal. Here, we
report the characterization of the first loss-of-function mutation in an RN
ase Hl gene in a metazoan organism, Drosophila melanogaster. Genetic studie
s of this mutant showed that this gene is essential for metamorphosis in Dr
osophila. However, disruption of the RNase HI gene does not affect prolifer
ation, but probably alters the regulation of gene expression. The lethal ph
enotype of this mutant also demonstrates that RNase HI activity in Drosophi
la cannot be provided by other cellular RNase H activities. Analysis of the
developmental and spatial expression profiles of a reporter gene placed un
der the control of the RNase HI promoter revealed increased expression in s
everal larval tissues. In salivary glands this increase was shown to be ind
ucible by treatment with ecdysone.