Control of translation is one of the major regulatory events in eukaryotic gene expression. Internal ribosome entry sites (IRES) were first discovered in picornavirus RNAs but it is now clear that IRESs are also present in the 5’ untranslated region of many eukaryotic genes including those encoding: growth factors e.g. VEGF, FGF2 and PDGF; genes whose protein products are associated with apoptosis e.g. Apaf-1, IXAP;transcription factors e.g. c- myc; the potassium channel Kv1.4. IRES allows the ribosomes to be recruited to an initiator AUG, which is some distance from the 5' end of the message RNA to bypass the Kozak scanning mechanism.. In the Kozak scanning model, the 40S ribosomal subunit bearing Met-tRNAmet and initiation factors, binds near the capped 5’end of the mRNA and travels along the mRNA until it comes to the first AUG. IRES-dependent initiation of protein synthesis occurs during apoptosis or some viral infection (e.g., picornavirus). A component of the cap-binding complex eIF-4F, translation initiation factor eIF-4G, is cleaved (by caspases or viral protein 2A) to give a modified form of cap-binding complex that is cap-independent.
Contributor: Joseph Chuang, PhD
REFERENCES: Chappell SA et al. A mutation in the c-myc-IRES leads to enhanced internal ribosome entry in multiple myeloma: a novel mechanism of oncogene de-regulation. Oncogene. 2000 Sep 7;19(38):4437-40. Stoneley M et al. c-Myc protein synthesis is initiated from the internal ribosome entry segment during apoptosis. Mol Cell Biol. 2000 Feb;20(4):1162-9. Vagner S et al. Irresistible IRES. Attracting the translation machinery to internal ribosome entry sites. EMBO Rep. 2001 Oct;2(10):893-8. Review.
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