Key result
Expression of Dcp1a induces translational arrest and restricts poliovirus infection through PKR activation, a process requiring the N-terminal EVH1 domain of Dcp1a.
Dcp1a expression induces a translation blockade via PKR activation, suggesting a novel signaling link between RNA degradation/decapping and translation regulation.
Links RNA decapping to antiviral translation control; extends preclinical understanding but leaves open clinical translation.
We have shown previously that poliovirus infection disrupts cytoplasmic P-bodies in infected mammalian cells. During the infectious cycle, poliovirus causes the directed cleavage of Dcp1a and Pan3, coincident with the dispersion of P-bodies. We now show that expression of Dcp1a prior to infection, surprisingly, restricts poliovirus infection. This inhibition of infection was independent of P-body formation because expression of GFP-Dcp1a mutants that cannot enter P-bodies restricted poliovirus infection similar to wild-type GFP-Dcp1a. Expression of wild-type or mutant GFP-Dcp1a induced phosphorylation of eIF2α through the eIF2α kinase protein kinase R (PKR). Activation of PKR required the amino-terminal EVH1 domain of Dcp1a. This PKR-induced translational inhibition appears to be specific to Dcp1a because the expression of other P-body components, Pan2, Pan3, Ccr4, or Caf1, did not result in the inhibition of poliovirus gene expression or induce eIF2α phosphorylation. The translation blockade induced by Dcp1a expression suggests novel signaling linking RNA degradation/decapping and regulation of translation.
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Dougherty et al. (2014) studied Poliovirus infection and cellular translation regulation. GFP-Dcp1a expression vs. GFP expression or untreated cells was evaluated on eIF2α phosphorylation and poliovirus protein expression. Expression of Dcp1a induces translational arrest and restricts poliovirus infection through PKR activation, a process requiring the N-terminal EVH1 domain of Dcp1a.
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