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mRNA decapping enzyme 1a (Dcp1a)-induced translational arrest through protein kinase R (PKR) activation requires the N-terminal enabled vasodilator-stimulated protein homology 1 (EVH1) domain.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2014 Feb 14; Vol. 289 (7), pp. 3936-49. Date of Electronic Publication: 2013 Dec 31. - Publication Year :
- 2014
-
Abstract
- 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.
- Subjects :
- Animals
Cell Line
Endoribonucleases genetics
Enzyme Activation genetics
Eukaryotic Initiation Factor-2 genetics
Eukaryotic Initiation Factor-2 metabolism
Exoribonucleases
Mice
Mice, Knockout
Mutation
Phosphorylation genetics
Poliomyelitis genetics
Poliomyelitis metabolism
Poliomyelitis pathology
Poliovirus genetics
Poliovirus metabolism
Protein Structure, Tertiary
Proteins genetics
Proteins metabolism
Receptors, CCR4 genetics
Receptors, CCR4 metabolism
Repressor Proteins
Ribonucleases
Trans-Activators genetics
eIF-2 Kinase genetics
Endoribonucleases metabolism
Protein Biosynthesis physiology
RNA Stability physiology
Trans-Activators metabolism
eIF-2 Kinase metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1083-351X
- Volume :
- 289
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 24382890
- Full Text :
- https://doi.org/10.1074/jbc.M113.518191