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. 1990 Feb;9(2):551–558. doi: 10.1002/j.1460-2075.1990.tb08142.x

A novel type of + 1 frameshift suppressor: a base substitution in the anticodon stem of a yeast mitochondrial serine-tRNA causes frameshift suppression.

A Hüttenhofer 1, B Weiss-Brummer 1, G Dirheimer 1, R P Martin 1
PMCID: PMC551700  PMID: 1689242

Abstract

We have identified a spontaneous mitochondrial mutation, mfs-1 (mitochondrial frameshift suppressor-1), which suppresses a + 1 frameshift mutation localized in the yeast mitochondrial oxi1 gene. The suppressor strain exhibits a single base change (C to U) at position 42 of the mitochondrial serine-tRNA (UCN). To our knowledge, this is the first reported case showing that a mutation in the anticodon stem of a tRNA can cause frameshift suppression. The expression and aminoacylation of the mutant tRNASer(UCN) are not significantly affected. However, the base change at position 42 has two effects: first, residue U27 of the mutant tRNA is not modified to pseudouridine as observed in wild-type tRNASer(UCN). Second, the base change and/or the lack of modification of U27 leads to an alteration in the secondary/tertiary structure of the mutant tRNA. It is possible that there are such structural changes in the anticodon loop that enable the tRNA to read a four base codon, UCCA, thus restoring the wild-type reading frame.

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Selected References

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

  1. Alwine J. C., Kemp D. J., Stark G. R. Method for detection of specific RNAs in agarose gels by transfer to diazobenzyloxymethyl-paper and hybridization with DNA probes. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5350–5354. doi: 10.1073/pnas.74.12.5350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ayer D., Yarus M. The context effect does not require a fourth base pair. Science. 1986 Jan 24;231(4736):393–395. doi: 10.1126/science.3510456. [DOI] [PubMed] [Google Scholar]
  3. Björk G. R., Ericson J. U., Gustafsson C. E., Hagervall T. G., Jönsson Y. H., Wikström P. M. Transfer RNA modification. Annu Rev Biochem. 1987;56:263–287. doi: 10.1146/annurev.bi.56.070187.001403. [DOI] [PubMed] [Google Scholar]
  4. Bordonné R., Dirheimer G., Martin R. P. Transcription initiation and RNA processing of a yeast mitochondrial tRNA gene cluster. Nucleic Acids Res. 1987 Sep 25;15(18):7381–7394. doi: 10.1093/nar/15.18.7381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bossi L., Roth J. R. Four-base codons ACCA, ACCU and ACCC are recognized by frameshift suppressor sufJ. Cell. 1981 Aug;25(2):489–496. doi: 10.1016/0092-8674(81)90067-2. [DOI] [PubMed] [Google Scholar]
  6. Bossi L., Smith D. M. Suppressor sufJ: a novel type of tRNA mutant that induces translational frameshifting. Proc Natl Acad Sci U S A. 1984 Oct;81(19):6105–6109. doi: 10.1073/pnas.81.19.6105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Coen D., Deutsch J., Netter P., Petrochilo E., Slonimski P. P. Mitochondrial genetics. I. Methodology and phenomenology. Symp Soc Exp Biol. 1970;24:449–496. [PubMed] [Google Scholar]
  8. Cummins C. M., Donahue T. F., Culbertson M. R. Nucleotide sequence of the SUF2 frameshift suppressor gene of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1982 Jun;79(11):3565–3569. doi: 10.1073/pnas.79.11.3565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Curran J. F., Yarus M. Base substitutions in the tRNA anticodon arm do not degrade the accuracy of reading frame maintenance. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6538–6542. doi: 10.1073/pnas.83.17.6538. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Curran J. F., Yarus M. Reading frame selection and transfer RNA anticodon loop stacking. Science. 1987 Dec 11;238(4833):1545–1550. doi: 10.1126/science.3685992. [DOI] [PubMed] [Google Scholar]
  11. DeFranco D., Schmidt O., Söll D. Two control regions for eukaryotic tRNA gene transcription. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3365–3368. doi: 10.1073/pnas.77.6.3365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Fox T. D., Weiss-Brummer B. Leaky +1 and -1 frameshift mutations at the same site in a yeast mitochondrial gene. Nature. 1980 Nov 6;288(5786):60–63. doi: 10.1038/288060a0. [DOI] [PubMed] [Google Scholar]
  14. Gaber R. F., Culbertson M. R. Codon recognition during frameshift suppression in Saccharomyces cerevisiae. Mol Cell Biol. 1984 Oct;4(10):2052–2061. doi: 10.1128/mcb.4.10.2052. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gaber R. F., Culbertson M. R. The yeast frameshift suppressor gene SUF16-1 encodes an altered glycine tRNA containing the four-base anticodon 3'-CCCG-5'. Gene. 1982 Sep;19(2):163–172. doi: 10.1016/0378-1119(82)90002-6. [DOI] [PubMed] [Google Scholar]
  16. Hudspeth M. E., Ainley W. M., Shumard D. S., Butow R. A., Grossman L. I. Location and structure of the var1 gene on yeast mitochondrial DNA: nucleotide sequence of the 40.0 allele. Cell. 1982 Sep;30(2):617–626. doi: 10.1016/0092-8674(82)90258-6. [DOI] [PubMed] [Google Scholar]
  17. Hudspeth M. E., Shumard D. S., Tatti K. M., Grossman L. I. Rapid purification of yeast mitochondrial DNA in high yield. Biochim Biophys Acta. 1980 Dec 11;610(2):221–228. doi: 10.1016/0005-2787(80)90003-9. [DOI] [PubMed] [Google Scholar]
  18. Hughes D., Atkins J. F., Thompson S. Mutants of elongation factor Tu promote ribosomal frameshifting and nonsense readthrough. EMBO J. 1987 Dec 20;6(13):4235–4239. doi: 10.1002/j.1460-2075.1987.tb02772.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Koski R. A., Clarkson S. G., Kurjan J., Hall B. D., Smith M. Mutations of the yeast SUP4 tRNATyr locus: transcription of the mutant genes in vitro. Cell. 1980 Nov;22(2 Pt 2):415–425. doi: 10.1016/0092-8674(80)90352-9. [DOI] [PubMed] [Google Scholar]
  20. Kutzleb R., Schweyen R. J., Kaudewitz F. Extrachromosomal inheritance of paromomycin resistance in Saccharomyces cerevisiae. Genetic and biochemical characterization of mutants. Mol Gen Genet. 1973 Sep 5;125(1):91–98. doi: 10.1007/BF00292984. [DOI] [PubMed] [Google Scholar]
  21. Locker J. Analytical and preparative electrophoresis of RNA in agarose-urea. Anal Biochem. 1979 Oct 1;98(2):358–367. doi: 10.1016/0003-2697(79)90154-4. [DOI] [PubMed] [Google Scholar]
  22. Martin R. P., Schneller J. M., Stahl A. J., Dirheimer G. Study of yeast mitochondrial tRNAs by two-dimensional polyacrylamide gel electrophoresis: characterization of isoaccepting species and search for imported cytoplasmic tRNAs. Nucleic Acids Res. 1977 Oct;4(10):3497–3510. doi: 10.1093/nar/4.10.3497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Martin R., Sibler A. P., Dirheimer G. The primary structures of three yeast mitochondrial serine tRNA isoacceptors. Biochimie. 1982 Nov-Dec;64(11-12):1073–1079. doi: 10.1016/s0300-9084(82)80389-1. [DOI] [PubMed] [Google Scholar]
  24. McClain W. H., Barrell B. G., Seidman J. G. Nucleotide alterations in bacteriophage T4 serine transfer RNA that affect the conversion of precursor RNA into transfer RNA. J Mol Biol. 1975 Dec 25;99(4):717–732. doi: 10.1016/s0022-2836(75)80181-1. [DOI] [PubMed] [Google Scholar]
  25. Messing J., Crea R., Seeburg P. H. A system for shotgun DNA sequencing. Nucleic Acids Res. 1981 Jan 24;9(2):309–321. doi: 10.1093/nar/9.2.309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. O'Mahony D. J., Mims B. H., Thompson S., Murgola E. J., Atkins J. F. Glycine tRNA mutants with normal anticodon loop size cause -1 frameshifting. Proc Natl Acad Sci U S A. 1989 Oct;86(20):7979–7983. doi: 10.1073/pnas.86.20.7979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Riddle D. L., Carbon J. Frameshift suppression: a nucleotide addition in the anticodon of a glycine transfer RNA. Nat New Biol. 1973 Apr 25;242(121):230–234. doi: 10.1038/newbio242230a0. [DOI] [PubMed] [Google Scholar]
  28. Roth J. R. Frameshift suppression. Cell. 1981 Jun;24(3):601–602. doi: 10.1016/0092-8674(81)90086-6. [DOI] [PubMed] [Google Scholar]
  29. Sanger F., Coulson A. R., Barrell B. G., Smith A. J., Roe B. A. Cloning in single-stranded bacteriophage as an aid to rapid DNA sequencing. J Mol Biol. 1980 Oct 25;143(2):161–178. doi: 10.1016/0022-2836(80)90196-5. [DOI] [PubMed] [Google Scholar]
  30. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Seong B. L., RajBhandary U. L. Escherichia coli formylmethionine tRNA: mutations in GGGCCC sequence conserved in anticodon stem of initiator tRNAs affect initiation of protein synthesis and conformation of anticodon loop. Proc Natl Acad Sci U S A. 1987 Jan;84(2):334–338. doi: 10.1073/pnas.84.2.334. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Sibler A. P., Dirheimer G., Martin R. P. The primary structure of yeast mitochondrial tyrosine tRNA. FEBS Lett. 1983 Feb 21;152(2):153–156. doi: 10.1016/0014-5793(83)80368-8. [DOI] [PubMed] [Google Scholar]
  33. Smith D., Yarus M. Transfer RNA structure and coding specificity. I. Evidence that a D-arm mutation reduces tRNA dissociation from the ribosome. J Mol Biol. 1989 Apr 5;206(3):489–501. doi: 10.1016/0022-2836(89)90496-8. [DOI] [PubMed] [Google Scholar]
  34. Sprinzl M., Moll J., Meissner F., Hartmann T. Compilation of tRNA sequences. Nucleic Acids Res. 1985;13 (Suppl):r1–49. doi: 10.1093/nar/13.suppl.r1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Tucker S. D., Murgola E. J., Pagel F. T. Missense and nonsense suppressors can correct frameshift mutations. Biochimie. 1989 Jun;71(6):729–739. doi: 10.1016/0300-9084(89)90089-8. [DOI] [PubMed] [Google Scholar]
  36. Weiss-Brummer B., Hüttenhofer A. The paromomycin resistance mutation (parr-454) in the 15 S rRNA gene of the yeast Saccharomyces cerevisiae is involved in ribosomal frameshifting. Mol Gen Genet. 1989 Jun;217(2-3):362–369. doi: 10.1007/BF02464905. [DOI] [PubMed] [Google Scholar]
  37. Weiss-Brummer B., Sakai H., Hüttenhofer A. A mitochondrial frameshift suppressor maps in the tRNASer-var1 region of the mitochondrial genome of the yeast S. cerevisiae. Curr Genet. 1989 Apr;15(4):239–246. doi: 10.1007/BF00447038. [DOI] [PubMed] [Google Scholar]
  38. Weiss-Brummer B., Sakai H., Kaudewitz F. A mitochondrial frameshift-suppressor (+1) [corrected] of the yeast S. cerevisiae maps in the mitochondrial 15S rRNA locus. Curr Genet. 1987;11(4):295–301. doi: 10.1007/BF00355403. [DOI] [PubMed] [Google Scholar]
  39. Weiss R., Gallant J. Mechanism of ribosome frameshifting during translation of the genetic code. 1983 Mar 31-Apr 6Nature. 302(5907):389–393. doi: 10.1038/302389a0. [DOI] [PubMed] [Google Scholar]
  40. Winey M., Mendenhall M. D., Cummins C. M., Culbertson M. R., Knapp G. Splicing of a yeast proline tRNA containing a novel suppressor mutation in the anticodon stem. J Mol Biol. 1986 Nov 5;192(1):49–63. doi: 10.1016/0022-2836(86)90463-8. [DOI] [PubMed] [Google Scholar]
  41. Zassenhaus H. P., Farrelly F., Hudspeth M. E., Grossman L. I., Butow R. A. Transcriptional analysis of the Saccharomyces cerevisiae mitochondrial var1 gene: anomalous hybridization of RNA from AT-rich regions. Mol Cell Biol. 1983 Sep;3(9):1615–1624. doi: 10.1128/mcb.3.9.1615. [DOI] [PMC free article] [PubMed] [Google Scholar]

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