Internal ribosome entry sites

Fig. 10 Screening hit and higher affinity benzimidazoles for HCV RNA internal ribosome entry site (IRES) IIA subdomain...

Figure 38-10. Picornavimses disrupt the 4F complex. The 4E-4G complex (4F) directs the 40S ribosomal subunit to the typical capped mRNA (see text). 4G alone is sufficient for targeting the 40S subunit to the internal ribosomal entry site (IRES) of viral mRNAs. To gain selective advantage, certain viruses (eg, poliovirus) have a protease that cleaves the 4E binding site from the amino terminal end of 4G. This truncated 4G can direct the 40S ribosomal subunit to mRNAs that have an IRES but not to those that have a cap. The widths of the arrows indicate the rate of translation initiation from the AUG codon in each example.

The catalytic activities of the fortified wheat germ cell-free systems supplemented with each fraction were investigated (Fig. 2). As shown in Fig. 2, only 0 - 40 % ammonium sulfate fraction showed an enhancement in DHFR protein synthesis. This enhancement of protein experimental results and the fact that the various eukaryotic initiation factors are contained in synthesis was also confirmed by SDS-PAGE and autoradiography (Fig. 3). From the above 0-40 % ammonium sulfate fraction [5, 6], it can be concluded that the amount of initiation factors in a conventionally prepared wheat germ cell-fi extract is deficient for the translation of DHFR with internal ribosome entry site. Therefore, it needs to supplement a wheat germ cell-free extract with the fraction containing the limited initiation factors for the efficient protein translation, and this fortified cell-free system can be easily made by simple... 

Hellen, C. U., and Samow, P. (2001). Internal ribosome entry sites in eukaryotic mRNA molecules. Genes Dev. 15, 1593—1612. 

Wilson, J. E., Powell, M. J., Hoover, S. E., and Samow, P. (2000). Naturally occurring dicistronic cricket paralysis virus RNA is regulated by two internal ribosome entry sites. Mol. Cell Biol. 20, 4990-4999. 

Qin, X., and Samow, P. (2004). Preferential translation of internal ribosome entry site-containing mRNAs during the mitotic cycle in mammalian cells. J. Biol. Chem. 279, 13721-13728. 

Holcik, M., and Korneluk, R. G. (2000). Functional characterization of the X-linked inhibitor of apoptosis (XIAP) internal ribosome entry site element Role of La autoantigen in XIAP translation. Mol. Cell Biol. 20, 4648-4657. 

Jan, E., and Samow, P. (2002). Factorless ribosome assembly on the internal ribosome entry site of cricket paralysis virus. J. Mol. Biol. 324, 889—902. 

Lomakin, I. B., Hellen, C. U., and Pestova, T. V. (2000). Physical association of eukaryotic initiation factor 4G (eIF4G) with eIF4A strongly enhances binding of eIF4G to the internal ribosomal entry site of encephalomyocarditis virus and is required for internal initiation of translation. Mol. Cell Biol. 20, 6019-6029. 

Pisarev, A. V., Shirokikh, N. E., and Hellen, C. U. (2005). Translation initiation by factor-independent binding of eukaryotic ribosomes to internal ribosomal entry sites. C R Biol. 328, 589-605. 

Kolupaeva, V.G., Fomakin, I.B., Pestova, T.V., and Hellen, C.U.T. (2003) Eukaryotic initiation factors 4G and 4A mediate conformational changes downstream of the initiation codon of the encephalomyocar-ditis virus internal ribosomal entry site. Mol. Cell. Biol. 23, 687-698. 

Many viral RNAs that are formed within eukaryotic cells lack a 5 cap. They depend upon internal ribosomal entry sites (IRESs). This has been studied most with picoma viruses.338 502 503 These viruses not only initiate translation at discrete sites in uncapped RNA but carry out a proteolytic cleavage of initiation factor 4G (Fig. 29-11), which seems to be necessary for initiation of viral-RNA translation.338 504 The IRES... 

Owens, G.C., Chappell, S.A., Mauro, V.P. and Edelman, G.M. (2001) Identification of two short internal ribosome entry sites selected from libraries of random oligonucleotides. Proc. Natl. Acad. Sci. USA, 98,1471-1476. 

Kruger, M., Beger, C., Li, Q.X., Welch, P.J., Tritz, R., Leavitt, M., Barber, J.R. and Wong-Staal, F. (2000) Identification of eIF2Bgamma and eIF2gamma as cofactors of hepatitis C virus internal ribosome entry site-mediated translation using a functional genomics approach. Proc. Natl. Acad. Sci. USA, 97, 8566-8571. 

Anwar, A., Ali, N., Tanveer, R. and Siddiqui, A. (2000) Demonstration of functional requirement of polypyrimidine tract-binding protein by SELEX RNA during hepatitis C virus internal ribosome entry site-mediated translation initiation. J. Biol. Chem., 275, 34231-34235. 

IRES, Internal ribosomal entry site, 8 Isolated liver perfusion, 419... 

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