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. 1987 Feb;6(2):409–417. doi: 10.1002/j.1460-2075.1987.tb04770.x

A novel endoribonuclease cleaves at a priming site of mouse mitochondrial DNA replication.

D D Chang, D A Clayton
PMCID: PMC553411  PMID: 3582365

Abstract

Priming at the mouse mitochondrial origin of heavy-strand DNA replication is effected by transcripts from the light-strand promoter. The transition from RNA synthesis to DNA synthesis occurs at specific locations between 75 and 165 nucleotides downstream from the transcriptional initiation site. We have identified and partially purified an endonucleolytic activity that cleaves RNA accurately near one of these transition sites; this finding implies a role of specific RNA processing in DNA replication. Cleavage products possess 5'-phosphoryl and 3'-hydroxyl termini. Heterologous assays using mouse or human mitochondrial endoribonuclease with substrates containing the sequences of the human or mouse mitochondrial origins of heavy-strand DNA replication suggest that selection of the cleavage site is guided by sequences adjacent to the actual position of cleavage.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson S., Bankier A. T., Barrell B. G., de Bruijn M. H., Coulson A. R., Drouin J., Eperon I. C., Nierlich D. P., Roe B. A., Sanger F. Sequence and organization of the human mitochondrial genome. Nature. 1981 Apr 9;290(5806):457–465. doi: 10.1038/290457a0. [DOI] [PubMed] [Google Scholar]
  2. Bibb M. J., Van Etten R. A., Wright C. T., Walberg M. W., Clayton D. A. Sequence and gene organization of mouse mitochondrial DNA. Cell. 1981 Oct;26(2 Pt 2):167–180. doi: 10.1016/0092-8674(81)90300-7. [DOI] [PubMed] [Google Scholar]
  3. Birnstiel M. L., Busslinger M., Strub K. Transcription termination and 3' processing: the end is in site! Cell. 1985 Jun;41(2):349–359. doi: 10.1016/s0092-8674(85)80007-6. [DOI] [PubMed] [Google Scholar]
  4. Cantor C. R., Efstratiadis A. Possible structures of homopurine-homopyrimidine S1-hypersensitive sites. Nucleic Acids Res. 1984 Nov 12;12(21):8059–8072. doi: 10.1093/nar/12.21.8059. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chang D. D., Clayton D. A. Precise assignment of the light-strand promoter of mouse mitochondrial DNA: a functional promoter consists of multiple upstream domains. Mol Cell Biol. 1986 Sep;6(9):3253–3261. doi: 10.1128/mcb.6.9.3253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chang D. D., Clayton D. A. Priming of human mitochondrial DNA replication occurs at the light-strand promoter. Proc Natl Acad Sci U S A. 1985 Jan;82(2):351–355. doi: 10.1073/pnas.82.2.351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chang D. D., Hauswirth W. W., Clayton D. A. Replication priming and transcription initiate from precisely the same site in mouse mitochondrial DNA. EMBO J. 1985 Jun;4(6):1559–1567. doi: 10.1002/j.1460-2075.1985.tb03817.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chomyn A., Mariottini P., Cleeter M. W., Ragan C. I., Matsuno-Yagi A., Hatefi Y., Doolittle R. F., Attardi G. Six unidentified reading frames of human mitochondrial DNA encode components of the respiratory-chain NADH dehydrogenase. Nature. 1985 Apr 18;314(6012):592–597. doi: 10.1038/314592a0. [DOI] [PubMed] [Google Scholar]
  9. Clayton D. A. Replication of animal mitochondrial DNA. Cell. 1982 Apr;28(4):693–705. doi: 10.1016/0092-8674(82)90049-6. [DOI] [PubMed] [Google Scholar]
  10. Donis-Keller H., Maxam A. M., Gilbert W. Mapping adenines, guanines, and pyrimidines in RNA. Nucleic Acids Res. 1977 Aug;4(8):2527–2538. doi: 10.1093/nar/4.8.2527. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. England T. E., Uhlenbeck O. C. 3'-terminal labelling of RNA with T4 RNA ligase. Nature. 1978 Oct 12;275(5680):560–561. doi: 10.1038/275560a0. [DOI] [PubMed] [Google Scholar]
  12. Garriga G., Lambowitz A. M., Inoue T., Cech T. R. Mechanism of recognition of the 5' splice site in self-splicing group I introns. Nature. 1986 Jul 3;322(6074):86–89. doi: 10.1038/322086a0. [DOI] [PubMed] [Google Scholar]
  13. Garriga G., Lambowitz A. M. RNA splicing in neurospora mitochondria: self-splicing of a mitochondrial intron in vitro. Cell. 1984 Dec;39(3 Pt 2):631–641. doi: 10.1016/0092-8674(84)90470-7. [DOI] [PubMed] [Google Scholar]
  14. Gegenheimer P., Apirion D. Processing of procaryotic ribonucleic acid. Microbiol Rev. 1981 Dec;45(4):502–541. doi: 10.1128/mr.45.4.502-541.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gillum A. M., Clayton D. A. Mechanism of mitochondrial DNA replication in mouse L-cells: RNA priming during the initiation of heavy-strand synthesis. J Mol Biol. 1979 Dec 5;135(2):353–368. doi: 10.1016/0022-2836(79)90441-8. [DOI] [PubMed] [Google Scholar]
  16. Guerrier-Takada C., Gardiner K., Marsh T., Pace N., Altman S. The RNA moiety of ribonuclease P is the catalytic subunit of the enzyme. Cell. 1983 Dec;35(3 Pt 2):849–857. doi: 10.1016/0092-8674(83)90117-4. [DOI] [PubMed] [Google Scholar]
  17. Martens P. A., Clayton D. A. Mechanism of mitochondrial DNA replication in mouse L-cells: localization and sequence of the light-strand origin of replication. J Mol Biol. 1979 Dec 5;135(2):327–351. doi: 10.1016/0022-2836(79)90440-6. [DOI] [PubMed] [Google Scholar]
  18. Mason P. J., Elkington J. A., Lloyd M. M., Jones M. B., Williams J. G. Mutations downstream of the polyadenylation site of a Xenopus beta-globin mRNA affect the position but not the efficiency of 3' processing. Cell. 1986 Jul 18;46(2):263–270. doi: 10.1016/0092-8674(86)90743-9. [DOI] [PubMed] [Google Scholar]
  19. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  20. Melton D. A., Krieg P. A., Rebagliati M. R., Maniatis T., Zinn K., Green M. R. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984 Sep 25;12(18):7035–7056. doi: 10.1093/nar/12.18.7035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Moore C. L., Sharp P. A. Accurate cleavage and polyadenylation of exogenous RNA substrate. Cell. 1985 Jul;41(3):845–855. doi: 10.1016/s0092-8674(85)80065-9. [DOI] [PubMed] [Google Scholar]
  22. Peebles C. L., Gegenheimer P., Abelson J. Precise excision of intervening sequences from precursor tRNAs by a membrane-associated yeast endonuclease. Cell. 1983 Feb;32(2):525–536. doi: 10.1016/0092-8674(83)90472-5. [DOI] [PubMed] [Google Scholar]
  23. Pulleyblank D. E., Haniford D. B., Morgan A. R. A structural basis for S1 nuclease sensitivity of double-stranded DNA. Cell. 1985 Aug;42(1):271–280. doi: 10.1016/s0092-8674(85)80122-7. [DOI] [PubMed] [Google Scholar]
  24. Read S. M., Northcote D. H. Minimization of variation in the response to different proteins of the Coomassie blue G dye-binding assay for protein. Anal Biochem. 1981 Sep 1;116(1):53–64. doi: 10.1016/0003-2697(81)90321-3. [DOI] [PubMed] [Google Scholar]
  25. Silberklang M., Gillum A. M., RajBhandary U. L. Use of in vitro 32P labeling in the sequence analysis of nonradioactive tRNAs. Methods Enzymol. 1979;59:58–109. doi: 10.1016/0076-6879(79)59072-7. [DOI] [PubMed] [Google Scholar]
  26. Tapper D. P., Clayton D. A. Precise nucleotide location of the 5' ends of RNA-primed nascent light strands of mouse mitochondrial DNA. J Mol Biol. 1982 Nov 25;162(1):1–16. doi: 10.1016/0022-2836(82)90159-0. [DOI] [PubMed] [Google Scholar]
  27. Tapper D. P., Van Etten R. A., Clayton D. A. Isolation of mammalian mitochondrial DNA and RNA and cloning of the mitochondrial genome. Methods Enzymol. 1983;97:426–434. doi: 10.1016/0076-6879(83)97153-7. [DOI] [PubMed] [Google Scholar]
  28. Van Etten R. A., Walberg M. W., Clayton D. A. Precise localization and nucleotide sequence of the two mouse mitochondrial rRNA genes and three immediately adjacent novel tRNA genes. Cell. 1980 Nov;22(1 Pt 1):157–170. doi: 10.1016/0092-8674(80)90164-6. [DOI] [PubMed] [Google Scholar]
  29. Walberg M. W., Clayton D. A. Sequence and properties of the human KB cell and mouse L cell D-loop regions of mitochondrial DNA. Nucleic Acids Res. 1981 Oct 24;9(20):5411–5421. doi: 10.1093/nar/9.20.5411. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Wickens M., Stephenson P. Role of the conserved AAUAAA sequence: four AAUAAA point mutants prevent messenger RNA 3' end formation. Science. 1984 Nov 30;226(4678):1045–1051. doi: 10.1126/science.6208611. [DOI] [PubMed] [Google Scholar]
  31. Wong T. W., Clayton D. A. In vitro replication of human mitochondrial DNA: accurate initiation at the origin of light-strand synthesis. Cell. 1985 Oct;42(3):951–958. doi: 10.1016/0092-8674(85)90291-0. [DOI] [PubMed] [Google Scholar]
  32. Zaug A. J., Cech T. R. The intervening sequence RNA of Tetrahymena is an enzyme. Science. 1986 Jan 31;231(4737):470–475. doi: 10.1126/science.3941911. [DOI] [PubMed] [Google Scholar]
  33. van der Horst G., Tabak H. F. Self-splicing of yeast mitochondrial ribosomal and messenger RNA precursors. Cell. 1985 Apr;40(4):759–766. doi: 10.1016/0092-8674(85)90335-6. [DOI] [PubMed] [Google Scholar]

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