Viruses, IRESs, and a universal translation initiation mechanism

Figures & data

Figure 1. Comparison of the four classes of viral IRESs and canonical cap-dependent translation.

Table 1. Bioengineering of novel and natural IRESs.

IRES	Approach	Methodology	Output	Regulation	Organism	Reference
Novel	Bottom-up	Randomized 18 nt	2 Novel IRESs	rRNA Base pairing	M. musculus	Owens et al., 2001
Novel	Bottom-up	Randomized 50 nt	2 Novel IRESs	Unknown	H. sapiens	Venkatesan et al., 2001
Novel	Bottom-up	Randomized 18 nt	56 Novel IRESs	rRNA Base pairing	S. cerevisiae	Zhou et al., 2003
EMCV	Top-down	Random Mutagenesis	12 IRES Variants	N/A	H. sapiens	Li et al., 2007
EMCV	Top-down	Directed Mutagenesis	24 IRES Variants	N/A	H. sapiens	Koh et al., 2013
FMDV	Top-down	Computational Design	Thermo-IRESs	Temperature	O. cuniculus	Garcia-Martin et al., 2016
IGR	Top-down	Rational Design	Ligand Responsive IRES	Ligand Binding	T. aestivum	Ogawa, 2011
IGR	Top-down	Rational Design	Ligand Responsive IRES	Ligand Binding	T. aestivum	Ogawa et al., 2017

Owens, G. C., Chappell, S. A., Mauro, V. P., & Edelman, G. M. (2001). Identification of two short internal ribosome entry sites selected from libraries of random oligonucleotides. Proceedings of the National Academy of Sciences USA, 98(4), 1471–1476.10.1073/pnas.98.4.1471

 PubMed Web of Science ®Google Scholar

Venkatesan, A., & Dasgupta, A. (2001). Novel fluorescence-based screen to identify small synthetic internal ribosome entry site elements. Molecular and Cellular Biology, 21(8), 2826–2837. doi:10.1128/mcb.21.8.2826-2837.2001

 PubMed Web of Science ®Google Scholar

Zhou, W., Edelman, G. M., & Mauro, V. P. (2003). Isolation and identification of short nucleotide sequences that affect translation initiation in Saccharomyces cerevisiae. Proceedings of the National Academy of Sciences USA, 100(8), 4457–4462. doi:10.1073/pnas.0437993100

 PubMed Web of Science ®Google Scholar

Li, J., Zhang, C., Jostock, T., & Dubel, S. (2007). Analysis of IgG heavy chain to light chain ratio with mutant Encephalomyocarditis virus internal ribosome entry site. Protein Engineering Design and Selection, 20(10), 491–496. doi:10.1093/protein/gzm038

 PubMed Web of Science ®Google Scholar

Koh, E. Y., Ho, S. C., Mariati, Z., Song, Z., Bi, X., Bardor, M., & Yang, Y. (2013). An internal ribosome entry site (IRES) mutant library for tuning expression level of multiple genes in mammalian cells. PLoS ONE, 8(12), e82100. doi:10.1371/journal.pone.0082100

 PubMed Web of Science ®Google Scholar

Garcia-Martin, J. A., Dotu, I., Fernandez-Chamorro, J., Lozano, G., Ramajo, J., Martinez-Salas, E., & Clote, P. (2016). RNAiFold2T: Constraint Programming design of thermo-IRES switches. Bioinformatics, 32(12), i360–i368. doi:10.1093/bioinformatics/btw265

 PubMed Web of Science ®Google Scholar

Ogawa, A. (2011). Rational design of artificial riboswitches based on ligand-dependent modulation of internal ribosome entry in wheat germ extract and their applications as label-free biosensors. RNA, 17(3), 478–488. doi:10.1261/rna.2433111

 PubMed Web of Science ®Google Scholar

Ogawa, A., Masuoka, H., & Ota, T. (2017). Artificial OFF-riboswitches that downregulate internal ribosome entry without hybridization switches in a eukaryotic cell-free translation system. ACS Synthetic Biology, 6(9), 1656–1662. doi:10.1021/acssynbio.7b00124

 PubMed Web of Science ®Google Scholar