Key result
Specific competition between the unrelated FMDV and BiP IRES elements impaired translation efficiency in a tricistronic vector, whereas no interference was detected with the HCV IRES.
Specific interference between unrelated IRES elements (FMDV and BiP) impairs translation efficiency, likely due to competition for common transacting factors.
IRES pairing in multicistronic vectors requires empirical testing; leaves open mechanisms of FMDV-BiP competition for shared factors.
Internal ribosome entry site (IRES) elements allow simultaneous synthesis of multiple proteins in eukaryotic cells. Here, two unrelated IRESs that perform efficiently in bicistronic constructs, the picornavirus foot-and-mouth disease virus (FMDV) and the cellular immunoglobulin heavy chain binding protein (BiP) IRES, were used to generate a tricistronic vector. Functional analysis of the tricistronic RNA evidenced that the efficiency of protein synthesis under the control of BiP IRES was lower than that of the FMDV IRES, relative to the efficiency measured in bicistronic vectors. A specific competition between these elements was verified using two separate mono- or bicistronic constructs in vivo and in vitro. In contrast, no interference was detected with the hepatitis C virus (HCV) IRES. The interference effect of FMDV IRES was observed in cis and trans, in support of competition for common transacting factors different than those used in cap- and HCV-dependent initiation.
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Reigadas et al. (2005) studied this question. Tricistronic vector with FMDV and BiP IRESs vs. Bicistronic vectors and HCV IRES was evaluated on Efficiency of protein synthesis and specific interference. Specific competition between the unrelated FMDV and BiP IRES elements impaired translation efficiency in a tricistronic vector, whereas no interference was detected with the HCV IRES.
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