Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Functional equivalence of human X– and Y–encoded isoforms of ribosomal protein S4 consistent with a role in Turner syndrome

Abstract

Several genes are found on both the human X and Y chromosomes in regions that do not recombine during male meiosis. In each case, nucleotide sequence analysis suggests that these X–Y gene pairs encode similar but nonidentical proteins. Here we show that the human Y– and X–encoded ribosomal proteins, RPS4Y and RPS4X, are interchangeable and provide an essential function: either protein rescued a mutant hamster cell line that was otherwise incapable of growth at modestly elevated temperatures. These findings are consistent with the hypothesis that RPS4 deficiency has a role in Turner syndrome, a complex human phenotype associated with monosomy X.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Ohno, S. Sex chromosomes and sex-linked genes. (Springer-Verlag, New York, 1967).

    Book  Google Scholar 

  2. Goodfellow, P.J., Darling, S.M., Thomas, N.S. & Goodfellow, P.N. A pseudoautosomal gene in man. Science 234, 740–743 (1986).

    Article  CAS  PubMed  Google Scholar 

  3. Gough, N.M. et al. Localization of the human GM-CSF receptor gene to the X-Y pseudoautosomal region. Nature 345, 734–736 (1990).

    Article  CAS  PubMed  Google Scholar 

  4. Ellison, J. et al. Directed isolation of human genes that escape X inactivation. Somat. Cell molec. Genet. 18, 259–268 (1992).

    Article  CAS  PubMed  Google Scholar 

  5. Schiebel, K., Weiss, B., Wöhrle, D. & Rappold, G. A human pseudoautosomal gene, ADP/ATP translocase, escapes X-inactivation whereas a homologue on Xq is subject to X-inactivation. Nature Genet. 3, 82–87 (1993).

    Article  CAS  PubMed  Google Scholar 

  6. Schneider-Gädicke, A., Beer-Romero, P., Brown, L.G., Nussbaum, R. & Page, D.C. ZFX has a gene structure similar to ZFY, the putative human sex determinant, and escapes X inactivation. Cell 57, 1247–1258 (1989).

    Article  PubMed  Google Scholar 

  7. Fisher, E.M.C. et al. Homologous ribosomal protein genes on the human X and Y chromosomes: Escape from X inactivation and possible implications for Turner syndrome. Cell 63, 1205–1218 (1990).

    Article  CAS  PubMed  Google Scholar 

  8. Salido, E.C., Yen, P.H., Koprivnikar, K., Yu, L.-C. & Shapiro, L.J. The human enamel protein gene amelogenin is expressed from both the X and the Y chromosomes. Am. J. hum. Genet. 50, 303–316 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Mitchell, M.J., Woods, D.R., Tucker, P.K., Opp, J.S. & Bishop, C.E. Homology of a candidate spermatogenic gene from the mouse Y chromosome to the ubiquitin-activating enzyme El. Nature 354, 483–486 (1991).

    Article  CAS  PubMed  Google Scholar 

  10. Kay, G.F. et al. A candidate spermatogenesis gene on the mouse Y chromosome is homologous to ubiquitin-activating enzyme E1. Nature 354, 486–489 (1991).

    Article  CAS  PubMed  Google Scholar 

  11. Wool, I.G., Chan, Y.-L., Paz, V. & Olvera, J. The primary structure of rat ribosomal proteins: The amino acid sequences of L27a and L28 and corrections in the sequences of S4 and S12. Biochim. Biophys. Acta 1050, 69–73 (1990).

    Article  CAS  PubMed  Google Scholar 

  12. Zinn, A.R. et al. Inactivation of the Rps4 gene on the mouse X chromosome. Genomics 11, 1097–1101 (1991).

    Article  CAS  PubMed  Google Scholar 

  13. Synetos, D., Dabeva, M.D. & Warner, J.R. The yeast ribosomal protein S7 and its genes. J. biol. Chem. 267, 3008–3013 (1992).

    CAS  PubMed  Google Scholar 

  14. Nishimoto, T. & Basilico, C. Analysis of a method for selecting temperature-sensitive mutants of BHK cells. Somat. Cell Genet. 4, 323–340 (1978).

    Article  CAS  PubMed  Google Scholar 

  15. Watanabe, M. et al. Molecular cloning of the human gene, CCG2, that complements the BHK-derived temperature-sensitive cell cycle mutant tsBN63—identity of CCG2 with the human X-chromosomal SCAR/RPS4X gene. J. cell Sci. 100, 35–43 (1991).

    PubMed  Google Scholar 

  16. Nishimoto, T. et al. Large-scale selection and analysis of temperature-sensitive mutants for cell reproduction from BHK cells. Somat. Cell Genet. 8, 811–824 (1982).

    Article  CAS  PubMed  Google Scholar 

  17. Ashworth, A., Rastan, S., Lovell-Badge, R. & Kay, G. X-chromosome inactivation may explain the difference in viability of XO humans and mice. Nature 351, 406–408 (1991).

    Article  CAS  PubMed  Google Scholar 

  18. Hamvas, R.M. et al. Rps4 maps near the inactivation center on the mouse X chromosome. Genomics 12, 363–367 (1992).

    Article  CAS  PubMed  Google Scholar 

  19. Hayakawa, H., Koike, G. & Sekiguchi, M. Expression and cloning of complementary DNA for a human enzyme that repairs O6-methylguanine in DNA. J. molec. Biol. 213, 739–747 (1990).

    Article  CAS  PubMed  Google Scholar 

  20. Woolford, J.J. The structure and biogenesis of yeast ribosomes. Adv. Genet. 29, 63–118 (1991).

    Article  CAS  PubMed  Google Scholar 

  21. Ford, C.E., Jones, K.W., Polani, P.E., De Almeida, J.C. & Briggs, J.H. A sex-chromosome anomaly in a case of gonadal dysgenesis (Turner's syndrome). Lancet i, 711–713 (1959).

    Article  Google Scholar 

  22. Lippe, B. Turner syndrome. Endocrinol. Metab. Clin. North Am. 20, 121–152 (1991).

    Article  CAS  PubMed  Google Scholar 

  23. Ferguson-Smith, M.A. Karyotype-phenotype correlations in gonadal dysgenesis and their bearing on the pathogenesis of malformations. J. med. Genet. 2, 142–155 (1965).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Page, D.C., Fisher, E.M., McGillivray, B. & Brown, L.G. Additional deletion in sex-determining region of human Y chromosome resolves paradox of X,t(Y;22) female. Nature 346, 279–281 (1990).

    Article  CAS  PubMed  Google Scholar 

  25. Ballabio, A. et al. Contiguous gene syndromes due to deletions in the distal short arm of the human X chromosome. Proc. natn. Acad. Sci. U.S.A. 86, 10001–10005 (1989).

    Article  CAS  Google Scholar 

  26. Levilliers, J., Quack, B., Weissenbach, J. & Petit, C. Exchange of terminal portions of X- and Y-chromosomal short arms in human XY females. Proc. natn. Acad. Sci. U.S.A. 86, 2296–2300 (1989).

    Article  CAS  Google Scholar 

  27. Just, W., Geerkens, C., Held, K.R. & Vogel, W. Expression of RPS4X in fibroblasts from patients with structural aberrations of the X chromosome. Hum. Genet. 89, 240–242 (1992).

    Article  CAS  PubMed  Google Scholar 

  28. Studier, F.W. & Moffatt, B.A. Use of bacteriophage T7 RNA polymerase to direct selective high-level expression of cloned genes. J. molec. Biol. 189, 113–130 (1986).

    Article  CAS  PubMed  Google Scholar 

  29. Szewczyk, B. & Kozloff, L.M. A method for the efficient blotting of strongly basic proteins from sodium dodecyl sulfate-polyacrylamide gels to nitrocellulose. Anal. Biochem. 150, 403–407 (1985).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Watanabe, M., Zinn, A., Page, D. et al. Functional equivalence of human X– and Y–encoded isoforms of ribosomal protein S4 consistent with a role in Turner syndrome. Nat Genet 4, 268–271 (1993). https://doi.org/10.1038/ng0793-268

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng0793-268

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing