Cellular and Molecular Life Sciences CMLS

, Volume 62, Issue 11, pp 1267–1274

Alternative splicing facilitates internal ribosome entry on the ornithine decarboxylase mRNA

Research Article

DOI: 10.1007/s00018-005-5020-8

Cite this article as:
Pyronnet, S., Pradayrol, L. & Sonenberg, N. CMLS, Cell. Mol. Life Sci. (2005) 62: 1267. doi:10.1007/s00018-005-5020-8

Abstract.

Ornithine decarboxylase (ODC) is the ratelimiting enzyme in the biosynthesis of polyamines, which are required for optimal cell growth and proliferation. ODC is overexpressed in many tumors and, conversely, its overexpression induces transformation. We have previously reported that ODC mRNA alternative splicing relieves the translation repression normally imposed by a long and structured 5′ untranslated region (UTR), and that the ODC 5′ UTR contains an internal ribosome entry site (IRES). Here we show that ODC IRES activity is enhanced following inclusion of alternative sequences generated by splicing at cryptic acceptor sites. Furthermore, the alternative ODC IRES is more sensitive to cell-cycledependent changes in the rate of translation. These findings uncover a new biological property of differentially spliced transcripts. This is the first example of alternative splicing that modulates mRNA translation through the cell cycle in a cap-independent manner.

Key words.

Ornithine decarboxylasetranslationcapinternal ribosome entry sitealternative splicingcell cycle

Copyright information

© Birkhäuser Verlag, Basel 2005

Authors and Affiliations

  1. 1.INSERM U531Institut Louis Bugnard IFR31Toulouse Cedex 4France
  2. 2.Department of BiochemistryMcGill UniversityMontrealCanada