Key result
Depletion of La autoantigen by siRNA or inhibition by a dominant-negative mutant caused a dramatic reduction in poliovirus and HCV IRES function and virus yield.
The La autoantigen is necessary for optimal IRES-dependent translation of poliovirus and HCV RNAs by stimulating 40S ribosomal subunit binding.
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La autoantigen may be an antiviral target for HCV and poliovirus; animal data leave open clinical translation.
Translation of poliovirus and hepatitis C virus (HCV) RNAs is initiated by recruitment of 40S ribosomes to an internal ribosome entry site (IRES) in the mRNA 5' untranslated region. Translation initiation of these RNAs is stimulated by noncanonical initiation factors called IRES trans-activating factors (ITAFs). The La autoantigen is such an ITAF, but functional evidence for the role of La in poliovirus and HCV translation in vivo is lacking. Here, by two methods using small interfering RNA and a dominant-negative mutant of La, we demonstrate that depletion of La causes a dramatic reduction in poliovirus IRES function in vivo. We also show that 40S ribosomal subunit binding to HCV and poliovirus IRESs in vitro is inhibited by a dominant-negative form of La. These results provide strong evidence for a function of the La autoantigen in IRES-dependent translation and define the step of translation which is stimulated by La.
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Costa‐Mattioli et al. (2004) studied Poliovirus and Hepatitis C virus translation. La autoantigen depletion (siRNA) or inhibition (LaDN) vs. Control siRNA or empty vector was evaluated on Poliovirus IRES function and virus yield. Depletion of La autoantigen by siRNA or inhibition by a dominant-negative mutant caused a dramatic reduction in poliovirus and HCV IRES function and virus yield.
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