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.

  • Short Report
  • Published:

Study of the 2719 mutant of the c-H-ras oncogene in a bi-intronic alternative splicing system

Abstract

C-H-ras proto-oncogene forms part of the signal transduction pathway of numerous external stimuli. This proto-oncogene is regulated by alternative splicing within its intron D due to the presence of the alternative intron D exon (IDX). The alternative splicing produces mRNA which encodes for the putative p19 protein, that lacks transforming potential. Herein, we demonstrated that SR proteins regulate the intron D splicing. Moreover, we studied the 2719 mutation of H-ras which has higher transforming potential than Ile12 and Val12 H-ras mutants and is also known to affect the 5′ splice site of the IDX. However, here we show that the 2719 mutant can still be spliced when the upstream 5′ splice-site is blocked. During these later studies, additionally, we generated a short 11 nucleotides 5′ terminal exon that was fully defined and spliced in a bi-intronic pre-mRNA. The definition of this mini-exon was also addressed in this work.

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

Access options

Buy this article

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

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  • Codony C, Guil S, Caudevilla C, Serra D, Asins G, Graessmann A, Hegardt FG, Bach-Elias M . 2001 Oncogene 20: 3683–3694

  • Cohen JB, Broz SD, Levinson AD . 1989 Cell 58: 461–472

  • Cohen JB, Levinson AD . 1988 Nature 334: 119–124

  • Crispino JD, Blencowe BJ, Sharp PA . 1994 Science 265: 1866–1869

  • Deng WP, Nickoloff JA . 1992 Anal. Biochem. 200: 81–88

  • Huang MY, Cohen JB . 1997 Oncol. Res. 9: 611–621

  • Izaurralde E, Lewis J, McGuigan C, Jankowska M, Darzynkiewicz E, Mattaj IW . 1994 Cell 78: 657–668

  • Lewis JD, Izaurralde E . 1997 Eur. J. Biochem. 247: 461–469

  • Lewis JD, Izaurralde E, Jarmolowski A, Mcguigan C, Mattaj IW . 1996 Genes Develop. 10: 1683–1698

  • MacMillan AM, McCaw PS, Crispino JD, Sharp PA . 1997 Proc. Natl. Acad. Sci. USA 94: 133–136

  • Mayeda A, Helfman DM, Krainer AR . 1993 Mol. Cell. Biol. 13: 2993–3001

  • Stickeler E, Kittrell F, Medina D, Berget SM . 1999 Oncogene 18: 3574–3582

  • Tarn WY, Steitz JA . 1994 Genes Dev. 8: 2704–2717

  • Vogel J, Hess WR, Borner T . 1997 Nucleic Acids Res. 25: 2030–2031

  • Zahler AM, Lane WS, Stolk JA, Roth MB . 1992 Genes Dev. 6: 837–847

  • Zhu L . 1996 Methods Mol. Biol. 57: 13–29

Download references

Acknowledgements

This work was supported by The Asociación Española contra el Cáncer, La Marató de TV3 and Fundación Ramón Areces and the Polish Committee for Scientific Research (KBN) #6 P04A 055 17. S Guil was a recipient of a BEFI fellowship. We thank Dr AD Levinson for donating the c-H-ras genes, and Drs I Mattaj and P Fortes for preparing the mock- and CBC-depleted extracts and rCBC for us.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Montse Bach-Elias.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Guil, S., Darzynkiewicz, E. & Bach-Elias, M. Study of the 2719 mutant of the c-H-ras oncogene in a bi-intronic alternative splicing system. Oncogene 21, 5649–5653 (2002). https://doi.org/10.1038/sj.onc.1205722

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1205722

Keywords

Search

Quick links