Failure to produce mitochondrial DNA results in embryonic lethality in Rnaseh1 null mice

Mol Cell. 2003 Mar;11(3):807-15. doi: 10.1016/s1097-2765(03)00088-1.


Although ribonucleases H (RNases H) have long been implicated in DNA metabolism, they are not required for viability in prokaryotes or unicellular eukaryotes. We generated Rnaseh1(-/-) mice to investigate the role of RNase H1 in mammals and observed developmental arrest at E8.5 in null embryos. A fraction of the mainly nuclear RNase H1 was targeted to mitochondria, and its absence in embryos resulted in a significant decrease in mitochondrial DNA content, leading to apoptotic cell death. This report links RNase H1 to generation of mitochondrial DNA, providing direct support for the strand-coupled mechanism of mitochondrial DNA replication. These findings also have important implications for therapy of mitochondrial dysfunctions and drug development for the structurally related RNase H of HIV.

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Animals
  • Apoptosis
  • Blotting, Southern
  • Cell Nucleus / metabolism
  • DNA / biosynthesis
  • DNA / metabolism
  • DNA, Mitochondrial / physiology*
  • Electron Transport
  • Genetic Vectors
  • Genotype
  • Homozygote
  • In Situ Nick-End Labeling
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Genetic
  • Molecular Sequence Data
  • Plasmids / metabolism
  • Polymerase Chain Reaction
  • Ribonuclease H / chemistry
  • Ribonuclease H / genetics*
  • Ribonuclease H / metabolism
  • Ribonuclease H / physiology*
  • Time Factors


  • DNA, Mitochondrial
  • DNA
  • Ribonuclease H