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