NSP3 (rotavirus)

Non Structural Rotavirus Protein 3
Identifiers
Symbol NSP3
PDB 1LJ2

Rotavirus protein NSP3 (NS34) is bound to the 3' end consensus sequence of viral mRNAs in infected cells.[1]

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.[2]

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.[3]

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.[4]

Site-directed mutagenesis and isothermal titration calorimetry documented that NSP3 and PABP use analogous eIF4G recognition strategies, despite marked differences in tertiary structure.[5]

Cellular vs Rotavirus Translation

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.[6]

References

  1. ↑ Poncet, D; Aponte, C; Cohen, J (1993). "Rotavirus protein NSP3 (NS34) is bound to the 3' end consensus sequence of viral mRNAs in infected cells" (Free full text). Journal of Virology 67 (6): 3159–65. PMC 237654. PMID 8388495.
  2. ↑ Poncet, D; Laurent, S; Cohen, J (1994). "Four nucleotides are the minimal requirement for RNA recognition by rotavirus non-structural protein NSP3" (Free full text). The EMBO Journal 13 (17): 4165–73. PMC 395339. PMID 8076612.
  3. ↑ Piron, M; Vende, P; Cohen, J; Poncet, D (1998). "Rotavirus RNA-binding protein NSP3 interacts with eIF4GI and evicts the poly(A) binding protein from eIF4F" (Free full text). The EMBO Journal 17 (19): 5811–21. doi:10.1093/emboj/17.19.5811. PMC 1170909. PMID 9755181.
  4. ↑ Vende, P; Piron, M; Castagné, N; Poncet, D (2000). "Efficient Translation of Rotavirus mRNA Requires Simultaneous Interaction of NSP3 with the Eukaryotic Translation Initiation Factor eIF4G and the mRNA 3′ End" (Free full text). Journal of Virology 74 (15): 7064–71. doi:10.1128/JVI.74.15.7064-7071.2000. PMC 112224. PMID 10888646.
  5. ↑ Groft, CM; Burley, SK (2002). "Recognition of eIF4G by rotavirus NSP3 reveals a basis for mRNA circularization". Molecular Cell 9 (6): 1273–83. doi:10.1016/S1097-2765(02)00555-5. PMID 12086624.
  6. ↑ Vitour, D; Lindenbaum, P; Vende, P; Becker, MM; Poncet, D (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" (Free full text). Journal of Virology 78 (8): 3851–62. doi:10.1128/JVI.78.8.3851-3862.2004. PMC 374268. PMID 15047801.
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