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NSP3 (rotavirus)

NSP3 (rotavirus)

Cellular vs Rotavirus Translation

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 nonstructural 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.

References

References

  1. (June 1993). "Rotavirus protein NSP3 (NS34) is bound to the 3' end consensus sequence of viral mRNAs in infected cells". Journal of Virology.
  2. (September 1994). "Four nucleotides are the minimal requirement for RNA recognition by rotavirus non-structural protein NSP3". The EMBO Journal.
  3. (October 1998). "Rotavirus RNA-binding protein NSP3 interacts with eIF4GI and evicts the poly(A) binding protein from eIF4F". The EMBO Journal.
  4. (August 2000). "Efficient translation of rotavirus mRNA requires simultaneous interaction of NSP3 with the eukaryotic translation initiation factor eIF4G and the mRNA 3' end". Journal of Virology.
  5. (June 2002). "Recognition of eIF4G by rotavirus NSP3 reveals a basis for mRNA circularization". Molecular Cell.
  6. (April 2004). "RoXaN, a novel cellular protein containing TPR, LD, and zinc finger motifs, forms a ternary complex with eukaryotic initiation factor 4G and rotavirus NSP3". Journal of Virology.
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