Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1996 Apr 2;93(7):2755–2758. doi: 10.1073/pnas.93.7.2755

Protein synthesis editing by a DNA aptamer.

S P Hale 1, P Schimmel 1
PMCID: PMC39704  PMID: 8610114

Abstract

Potential errors in decoding genetic information are corrected by tRNA-dependent amino acid recognition processes manifested through editing reactions. One example is the rejection of difficult-to-discriminate misactivated amino acids by tRNA synthetases through hydrolytic reactions. Although several crystal structures of tRNA synthetases and synthetase-tRNA complexes exist, none of them have provided insight into the editing reactions. Other work suggested that editing required active amino acid acceptor hydroxyl groups at the 3' end of a tRNA effector. We describe here the isolation of a DNA aptamer that specifically induced hydrolysis of a misactivated amino acid bound to a tRNA synthetase. The aptamer had no effect on the stability of the correctly activated amino acid and was almost as efficient as the tRNA for inducing editing activity. The aptamer has no sequence similarity to that of the tRNA effector and cannot be folded into a tRNA-like structure. These and additional data show that active acceptor hydroxyl groups in a tRNA effector and a tRNA-like structure are not essential for editing. Thus, specific bases in a nucleic acid effector trigger the editing response.

Full text

PDF
2755

Images in this article

2756Fig. 3
on p.2756
2757Fig. 4
on p.2757

Selected References

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

  1. Arnez J. G., Harris D. C., Mitschler A., Rees B., Francklyn C. S., Moras D. Crystal structure of histidyl-tRNA synthetase from Escherichia coli complexed with histidyl-adenylate. EMBO J. 1995 Sep 1;14(17):4143–4155. doi: 10.1002/j.1460-2075.1995.tb00088.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baldwin A. N., Berg P. Transfer ribonucleic acid-induced hydrolysis of valyladenylate bound to isoleucyl ribonucleic acid synthetase. J Biol Chem. 1966 Feb 25;241(4):839–845. [PubMed] [Google Scholar]
  3. Bock L. C., Griffin L. C., Latham J. A., Vermaas E. H., Toole J. J. Selection of single-stranded DNA molecules that bind and inhibit human thrombin. Nature. 1992 Feb 6;355(6360):564–566. doi: 10.1038/355564a0. [DOI] [PubMed] [Google Scholar]
  4. Brick P., Bhat T. N., Blow D. M. Structure of tyrosyl-tRNA synthetase refined at 2.3 A resolution. Interaction of the enzyme with the tyrosyl adenylate intermediate. J Mol Biol. 1989 Jul 5;208(1):83–98. doi: 10.1016/0022-2836(89)90090-9. [DOI] [PubMed] [Google Scholar]
  5. Coombs K. M., Fields B. N., Harrison S. C. Crystallization of the reovirus type 3 Dearing core. Crystal packing is determined by the lambda 2 protein. J Mol Biol. 1990 Sep 5;215(1):1–5. doi: 10.1016/s0022-2836(05)80089-0. [DOI] [PubMed] [Google Scholar]
  6. Cramer F., Englisch U., Freist W., Sternbach H. Aminoacylation of tRNAs as critical step of protein biosynthesis. Biochimie. 1991 Jul-Aug;73(7-8):1027–1035. doi: 10.1016/0300-9084(91)90144-p. [DOI] [PubMed] [Google Scholar]
  7. Cusack S., Berthet-Colominas C., Härtlein M., Nassar N., Leberman R. A second class of synthetase structure revealed by X-ray analysis of Escherichia coli seryl-tRNA synthetase at 2.5 A. Nature. 1990 Sep 20;347(6290):249–255. doi: 10.1038/347249a0. [DOI] [PubMed] [Google Scholar]
  8. Doublié S., Bricogne G., Gilmore C., Carter C. W., Jr Tryptophanyl-tRNA synthetase crystal structure reveals an unexpected homology to tyrosyl-tRNA synthetase. Structure. 1995 Jan 15;3(1):17–31. doi: 10.1016/s0969-2126(01)00132-0. [DOI] [PubMed] [Google Scholar]
  9. Eldred E. W., Schimmel P. R. Rapid deacylation by isoleucyl transfer ribonucleic acid synthetase of isoleucine-specific transfer ribonucleic acid aminoacylated with valine. J Biol Chem. 1972 May 10;247(9):2961–2964. [PubMed] [Google Scholar]
  10. Ellington A. D., Szostak J. W. In vitro selection of RNA molecules that bind specific ligands. Nature. 1990 Aug 30;346(6287):818–822. doi: 10.1038/346818a0. [DOI] [PubMed] [Google Scholar]
  11. Eriani G., Delarue M., Poch O., Gangloff J., Moras D. Partition of tRNA synthetases into two classes based on mutually exclusive sets of sequence motifs. Nature. 1990 Sep 13;347(6289):203–206. doi: 10.1038/347203a0. [DOI] [PubMed] [Google Scholar]
  12. Fersht A. R. Editing mechanisms in protein synthesis. Rejection of valine by the isoleucyl-tRNA synthetase. Biochemistry. 1977 Mar 8;16(5):1025–1030. doi: 10.1021/bi00624a034. [DOI] [PubMed] [Google Scholar]
  13. Freist W. Mechanisms of aminoacyl-tRNA synthetases: a critical consideration of recent results. Biochemistry. 1989 Aug 22;28(17):6787–6795. doi: 10.1021/bi00443a001. [DOI] [PubMed] [Google Scholar]
  14. Jakubowski H., Goldman E. Editing of errors in selection of amino acids for protein synthesis. Microbiol Rev. 1992 Sep;56(3):412–429. doi: 10.1128/mr.56.3.412-429.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Logan D. T., Mazauric M. H., Kern D., Moras D. Crystal structure of glycyl-tRNA synthetase from Thermus thermophilus. EMBO J. 1995 Sep 1;14(17):4156–4167. doi: 10.1002/j.1460-2075.1995.tb00089.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mosyak L., Reshetnikova L., Goldgur Y., Delarue M., Safro M. G. Structure of phenylalanyl-tRNA synthetase from Thermus thermophilus. Nat Struct Biol. 1995 Jul;2(7):537–547. doi: 10.1038/nsb0795-537. [DOI] [PubMed] [Google Scholar]
  17. Nureki O., Vassylyev D. G., Katayanagi K., Shimizu T., Sekine S., Kigawa T., Miyazawa T., Yokoyama S., Morikawa K. Architectures of class-defining and specific domains of glutamyl-tRNA synthetase. Science. 1995 Mar 31;267(5206):1958–1965. doi: 10.1126/science.7701318. [DOI] [PubMed] [Google Scholar]
  18. Onesti S., Miller A. D., Brick P. The crystal structure of the lysyl-tRNA synthetase (LysU) from Escherichia coli. Structure. 1995 Feb 15;3(2):163–176. doi: 10.1016/s0969-2126(01)00147-2. [DOI] [PubMed] [Google Scholar]
  19. Rich A., RajBhandary U. L. Transfer RNA: molecular structure, sequence, and properties. Annu Rev Biochem. 1976;45:805–860. doi: 10.1146/annurev.bi.45.070176.004105. [DOI] [PubMed] [Google Scholar]
  20. Riggs A. D., Suzuki H., Bourgeois S. Lac repressor-operator interaction. I. Equilibrium studies. J Mol Biol. 1970 Feb 28;48(1):67–83. doi: 10.1016/0022-2836(70)90219-6. [DOI] [PubMed] [Google Scholar]
  21. Robertson D. L., Joyce G. F. Selection in vitro of an RNA enzyme that specifically cleaves single-stranded DNA. Nature. 1990 Mar 29;344(6265):467–468. doi: 10.1038/344467a0. [DOI] [PubMed] [Google Scholar]
  22. Rould M. A., Perona J. J., Söll D., Steitz T. A. Structure of E. coli glutaminyl-tRNA synthetase complexed with tRNA(Gln) and ATP at 2.8 A resolution. Science. 1989 Dec 1;246(4934):1135–1142. doi: 10.1126/science.2479982. [DOI] [PubMed] [Google Scholar]
  23. Ruff M., Krishnaswamy S., Boeglin M., Poterszman A., Mitschler A., Podjarny A., Rees B., Thierry J. C., Moras D. Class II aminoacyl transfer RNA synthetases: crystal structure of yeast aspartyl-tRNA synthetase complexed with tRNA(Asp). Science. 1991 Jun 21;252(5013):1682–1689. doi: 10.1126/science.2047877. [DOI] [PubMed] [Google Scholar]
  24. Schimmel P. R., Söll D. Aminoacyl-tRNA synthetases: general features and recognition of transfer RNAs. Annu Rev Biochem. 1979;48:601–648. doi: 10.1146/annurev.bi.48.070179.003125. [DOI] [PubMed] [Google Scholar]
  25. Schmidt E., Schimmel P. Mutational isolation of a sieve for editing in a transfer RNA synthetase. Science. 1994 Apr 8;264(5156):265–267. doi: 10.1126/science.8146659. [DOI] [PubMed] [Google Scholar]
  26. Shepard A., Shiba K., Schimmel P. RNA binding determinant in some class I tRNA synthetases identified by alignment-guided mutagenesis. Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9964–9968. doi: 10.1073/pnas.89.20.9964. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Taiji M., Yokoyama S., Miyazawa T. Transacylation rates of (aminoacyl)adenosine moiety at the 3'-terminus of aminoacyl transfer ribonucleic acid. Biochemistry. 1983 Jun 21;22(13):3220–3225. doi: 10.1021/bi00282a028. [DOI] [PubMed] [Google Scholar]
  28. Tuerk C., Gold L. Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science. 1990 Aug 3;249(4968):505–510. doi: 10.1126/science.2200121. [DOI] [PubMed] [Google Scholar]
  29. Ueda H., Shoku Y., Hayashi N., Mitsunaga J., In Y., Doi M., Inoue M., Ishida T. X-ray crystallographic conformational study of 5'-O-[N-(L-alanyl)-sulfamoyl]adenosine, a substrate analogue for alanyl-tRNA synthetase. Biochim Biophys Acta. 1991 Oct 25;1080(2):126–134. doi: 10.1016/0167-4838(91)90138-p. [DOI] [PubMed] [Google Scholar]
  30. von der Haar F., Cramer F. Hydrolytic action of aminoacyl-tRNA synthetases from baker's yeast: "chemical proofreading" preventing acylation of tRNA(I1e) with misactivated valine. Biochemistry. 1976 Sep 7;15(18):4131–4138. doi: 10.1021/bi00663a034. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES