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Review
. 2005 Nov 28;33(20):6593-602.
doi: 10.1093/nar/gki958. Print 2005.

A second look at cellular mRNA sequences said to function as internal ribosome entry sites

Marilyn Kozak  1
Affiliations
Review

A second look at cellular mRNA sequences said to function as internal ribosome entry sites

Marilyn Kozak. Nucleic Acids Res. .

Abstract

This review takes a second look at a set of mRNAs that purportedly employ an alternative mechanism of initiation when cap-dependent translation is reduced during mitosis or stress conditions. A closer look is necessary because evidence cited in support of the internal initiation hypothesis is often flawed. When putative internal ribosome entry sequences (IRESs) are examined more carefully, they often turn out to harbor cryptic promoters or splice sites. This undermines the dicistronic assay, wherein IRES activity is measured by the ability to support translation of the 3' cistron. Most putative IRESs still have not been checked carefully to determine whether the dicistronic vector produces only the intended dicistronic mRNA. The widespread use of the pRF vector is a major problem because this vector, which has Renilla luciferase as the 5' cistron and firefly luciferase as the 3' cistron, has been found to generate spliced transcripts. RNA transfection assays could theoretically circumvent these problems, but most candidate IRESs score very weakly in that test. The practice of calling even very weak results 'positive' is one of the problems discussed herein. The extremely low efficiency of putative IRESs is inconsistent with their postulated biological roles.'

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References

    1. Komar A.A., Hatzoglou M. Internal ribosome entry sites in cellular mRNAs: mystery of their existence. J. Biol. Chem. 2005;280:23425–23428. - PubMed
    1. Nevins T.A., Harder Z.M., Korneluk R.G., Holčik M. Distinct regulation of IRES-mediated translation following cellular stress is mediated by apoptotic fragments of eIF4G family members eIF4GI and p97/DAP5/NAT1. J. Biol. Chem. 2003;278:3572–3579. - PubMed
    1. Coldwell M.J., Mitchell S.A., Stoneley M., MacFarlane M., Willis A.E. Initiation of Apaf-1 translation by internal ribosome entry. Oncogene. 2000;19:899–905. - PubMed
    1. Mitchell S.A., Brown E.C., Coldwell M.J., Jackson R.J., Willis A.E. Protein factor requirements of the Apaf-1 IRES: roles of polypyrimidine tract binding protein and upstream of N-ras. Mol. Cell. Biol. 2001;21:3364–3374. - PMC - PubMed
    1. Van Eden M.E., Byrd M.P., Sherrill K.W., Lloyd R.E. Demonstrating internal ribosome entry sites in eukaryotic mRNAs using stringent RNA test procedures. RNA. 2004;10:720–730. - PMC - PubMed

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