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. 1986 Jun;83(12):4360–4363. doi: 10.1073/pnas.83.12.4360

A model for the RNA-catalyzed replication of RNA.

T R Cech
PMCID: PMC323732  PMID: 2424025

Abstract

A shortened form of the self-splicing ribosomal RNA intervening sequence of Tetrahymena thermophila has enzymatic activity as a poly(cytidylic acid) polymerase [Zaug, A.J. & Cech, T.R. (1986) Science 231, 470-475]. Based on the known properties of this enzyme, a detailed model is developed for the template-dependent synthesis of RNA by an RNA polymerase itself made of RNA. The monomer units for RNA synthesis are tetra- and pentanucleotides of random base sequence. Polymerization occurs in a 5'-to-3' direction, and elongation rates are expected to approach two residues per minute. If the RNA enzyme could use another copy of itself as a template, RNA self-replication could be achieved. Thus, it seems possible that RNA catalysts might have played a part in prebiotic nucleic acid replication, prior to the availability of useful proteins.

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Selected References

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

  1. Altman S. Aspects of biochemical catalysis. Cell. 1984 Feb;36(2):237–239. doi: 10.1016/0092-8674(84)90216-2. [DOI] [PubMed] [Google Scholar]
  2. Been M. D., Cech T. R. Sites of circularization of the Tetrahymena rRNA IVS are determined by sequence and influenced by position and secondary structure. Nucleic Acids Res. 1985 Dec 9;13(23):8389–8408. doi: 10.1093/nar/13.23.8389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bridson P. K., Orgel L. E. Catalysis of accurate poly(C)-directed synthesis of 3'-5'-linked oligoguanylates by Zn2+. J Mol Biol. 1980 Dec 25;144(4):567–577. doi: 10.1016/0022-2836(80)90337-x. [DOI] [PubMed] [Google Scholar]
  4. Burke J. M., Irvine K. D., Kaneko K. J., Kerker B. J., Oettgen A. B., Tierney W. M., Williamson C. L., Zaug A. J., Cech T. R. Role of conserved sequence elements 9L and 2 in self-splicing of the Tetrahymena ribosomal RNA precursor. Cell. 1986 Apr 25;45(2):167–176. doi: 10.1016/0092-8674(86)90380-6. [DOI] [PubMed] [Google Scholar]
  5. Cech T. R. RNA splicing: three themes with variations. Cell. 1983 Oct;34(3):713–716. doi: 10.1016/0092-8674(83)90527-5. [DOI] [PubMed] [Google Scholar]
  6. Cech T. R. Self-splicing RNA: implications for evolution. Int Rev Cytol. 1985;93:3–22. doi: 10.1016/s0074-7696(08)61370-4. [DOI] [PubMed] [Google Scholar]
  7. Cech T. R., Zaug A. J., Grabowski P. J. In vitro splicing of the ribosomal RNA precursor of Tetrahymena: involvement of a guanosine nucleotide in the excision of the intervening sequence. Cell. 1981 Dec;27(3 Pt 2):487–496. doi: 10.1016/0092-8674(81)90390-1. [DOI] [PubMed] [Google Scholar]
  8. Chu F. K., Maley G. F., West D. K., Belfort M., Maley F. Characterization of the intron in the phage T4 thymidylate synthase gene and evidence for its self-excision from the primary transcript. Cell. 1986 Apr 25;45(2):157–166. doi: 10.1016/0092-8674(86)90379-x. [DOI] [PubMed] [Google Scholar]
  9. Crick F. H. The origin of the genetic code. J Mol Biol. 1968 Dec;38(3):367–379. doi: 10.1016/0022-2836(68)90392-6. [DOI] [PubMed] [Google Scholar]
  10. Darnell J. E., Doolittle W. F. Speculations on the early course of evolution. Proc Natl Acad Sci U S A. 1986 Mar;83(5):1271–1275. doi: 10.1073/pnas.83.5.1271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Davies R. W., Waring R. B., Ray J. A., Brown T. A., Scazzocchio C. Making ends meet: a model for RNA splicing in fungal mitochondria. Nature. 1982 Dec 23;300(5894):719–724. doi: 10.1038/300719a0. [DOI] [PubMed] [Google Scholar]
  12. Eigen M. Selforganization of matter and the evolution of biological macromolecules. Naturwissenschaften. 1971 Oct;58(10):465–523. doi: 10.1007/BF00623322. [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. Guerrier-Takada C., Altman S. Catalytic activity of an RNA molecule prepared by transcription in vitro. Science. 1984 Jan 20;223(4633):285–286. doi: 10.1126/science.6199841. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Inoue T., Joyce G. F., Grzeskowiak K., Orgel L. E., Brown J. M., Reese C. B. Template-directed synthesis on the pentanucleotide CpCpGpCpC. J Mol Biol. 1984 Sep 25;178(3):669–676. doi: 10.1016/0022-2836(84)90244-4. [DOI] [PubMed] [Google Scholar]
  17. Inoue T., Orgel L. E. A nonenzymatic RNA polymerase model. Science. 1983 Feb 18;219(4586):859–862. doi: 10.1126/science.6186026. [DOI] [PubMed] [Google Scholar]
  18. Inoue T., Orgel L. E. Oligomerization of (guanosine 5'-phosphor)-2-methylimidazolide on poly(C). An RNA polymerase model. J Mol Biol. 1982 Nov 25;162(1):201–217. doi: 10.1016/0022-2836(82)90169-3. [DOI] [PubMed] [Google Scholar]
  19. Inoue T., Sullivan F. X., Cech T. R. Intermolecular exon ligation of the rRNA precursor of Tetrahymena: oligonucleotides can function as 5' exons. Cell. 1985 Dec;43(2 Pt 1):431–437. doi: 10.1016/0092-8674(85)90173-4. [DOI] [PubMed] [Google Scholar]
  20. Kramer F. R., Mills D. R. Secondary structure formation during RNA synthesis. Nucleic Acids Res. 1981 Oct 10;9(19):5109–5124. doi: 10.1093/nar/9.19.5109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kruger K., Grabowski P. J., Zaug A. J., Sands J., Gottschling D. E., Cech T. R. Self-splicing RNA: autoexcision and autocyclization of the ribosomal RNA intervening sequence of Tetrahymena. Cell. 1982 Nov;31(1):147–157. doi: 10.1016/0092-8674(82)90414-7. [DOI] [PubMed] [Google Scholar]
  22. Lewin R. RNA can be a catalyst. Science. 1982 Nov 26;218(4575):872–874. doi: 10.1126/science.6182615. [DOI] [PubMed] [Google Scholar]
  23. Marsh T. L., Pace N. R. Ribonuclease P catalysis differs from ribosomal RNA self-splicing. Science. 1985 Jul 5;229(4708):79–81. doi: 10.1126/science.4012313. [DOI] [PubMed] [Google Scholar]
  24. Michel F., Dujon B. Conservation of RNA secondary structures in two intron families including mitochondrial-, chloroplast- and nuclear-encoded members. EMBO J. 1983;2(1):33–38. doi: 10.1002/j.1460-2075.1983.tb01376.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Mills D. R., Kramer F. R., Spiegelman S. Complete nucleotide sequence of a replicating RNA molecule. Science. 1973 Jun 1;180(4089):916–927. doi: 10.1126/science.180.4089.916. [DOI] [PubMed] [Google Scholar]
  26. Noller H. F. Structure of ribosomal RNA. Annu Rev Biochem. 1984;53:119–162. doi: 10.1146/annurev.bi.53.070184.001003. [DOI] [PubMed] [Google Scholar]
  27. Orgel L. E. Evolution of the genetic apparatus. J Mol Biol. 1968 Dec;38(3):381–393. doi: 10.1016/0022-2836(68)90393-8. [DOI] [PubMed] [Google Scholar]
  28. Peebles C. L., Perlman P. S., Mecklenburg K. L., Petrillo M. L., Tabor J. H., Jarrell K. A., Cheng H. L. A self-splicing RNA excises an intron lariat. Cell. 1986 Jan 31;44(2):213–223. doi: 10.1016/0092-8674(86)90755-5. [DOI] [PubMed] [Google Scholar]
  29. Price J. V., Kieft G. L., Kent J. R., Sievers E. L., Cech T. R. Sequence requirements for self-splicing of the Tetrahymena thermophila pre-ribosomal RNA. Nucleic Acids Res. 1985 Mar 25;13(6):1871–1889. doi: 10.1093/nar/13.6.1871. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Reanney D. RNA splicing and polynucleotide evolution. Nature. 1979 Feb 22;277(5698):598–600. doi: 10.1038/277598b0. [DOI] [PubMed] [Google Scholar]
  31. Sharp P. A. On the origin of RNA splicing and introns. Cell. 1985 Sep;42(2):397–400. doi: 10.1016/0092-8674(85)90092-3. [DOI] [PubMed] [Google Scholar]
  32. Sullivan F. X., Cech T. R. Reversibility of cyclization of the Tetrahymena rRNA intervening sequence: implication for the mechanism of splice site choice. Cell. 1985 Sep;42(2):639–648. doi: 10.1016/0092-8674(85)90121-7. [DOI] [PubMed] [Google Scholar]
  33. Usher D. A., McHale A. H. Nonenzymic joining of oligoadenylates on a polyuridylic acid template. Science. 1976 Apr 2;192(4234):53–54. doi: 10.1126/science.1257755. [DOI] [PubMed] [Google Scholar]
  34. Waring R. B., Davies R. W. Assessment of a model for intron RNA secondary structure relevant to RNA self-splicing--a review. Gene. 1984 Jun;28(3):277–291. doi: 10.1016/0378-1119(84)90145-8. [DOI] [PubMed] [Google Scholar]
  35. Waring R. B., Ray J. A., Edwards S. W., Scazzocchio C., Davies R. W. The Tetrahymena rRNA intron self-splices in E. coli: in vivo evidence for the importance of key base-paired regions of RNA for RNA enzyme function. Cell. 1985 Feb;40(2):371–380. doi: 10.1016/0092-8674(85)90151-5. [DOI] [PubMed] [Google Scholar]
  36. Waring R. B., Scazzocchio C., Brown T. A., Davies R. W. Close relationship between certain nuclear and mitochondrial introns. Implications for the mechanism of RNA splicing. J Mol Biol. 1983 Jul 5;167(3):595–605. doi: 10.1016/s0022-2836(83)80100-4. [DOI] [PubMed] [Google Scholar]
  37. Zaug A. J., Cech T. R. Oligomerization of intervening sequence RNA molecules in the absence of proteins. Science. 1985 Sep 13;229(4718):1060–1064. doi: 10.1126/science.2412290. [DOI] [PubMed] [Google Scholar]
  38. 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]
  39. 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]
  40. van der Veen R., Arnberg A. C., van der Horst G., Bonen L., Tabak H. F., Grivell L. A. Excised group II introns in yeast mitochondria are lariats and can be formed by self-splicing in vitro. Cell. 1986 Jan 31;44(2):225–234. doi: 10.1016/0092-8674(86)90756-7. [DOI] [PubMed] [Google Scholar]

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