Symbol NSP3 | PDB 1LJ2 | |
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Rotavirus protein NSP3 (NS34) is bound to the 3' end consensus sequence of viral mRNAs in infected cells.
Four nucleotides are the minimal requirement for RNA recognition by rotavirus non-structural protein NSP3: using short oligoribonucleotides, it was established that the minimal RNA sequence required for binding of NSP3A is GACC.
Rotavirus RNA-binding protein NSP3 interacts with eIF4GI and evicts the poly(A)-binding protein from eIF4F. And NSP3A, by taking the place of PABP on eIF4GI, is responsible for the shut-off of cellular protein synthesis.
Expression of NSP3 in mammalian cells allows the efficient translation of virus-like mRNA: NSP3 forms a link between viral mRNA and the cellular translation machinery and hence is a functional analogue of cellular poly(A)-binding protein.
Site-directed mutagenesis and isothermal titration calorimetry documented that NSP3 and PABP use analogous eIF4G recognition strategies, despite marked differences in tertiary structure.
Using the yeast two-hybrid assay, RoXan a novel cellular protein was found to bind NSP3. The interaction between NSP3 and RoXaN does not impair the interaction between NSP3 and eIF4GI, and a ternary complex made of NSP3, RoXaN, and eIF4G I can be detected in rotavirus-infected cells, implicating RoXaN in translation regulation.