Rotavirus
''Rotavirus'' is a genus of double-stranded RNA viruses in the family ''Reoviridae''. Rotaviruses are the most common cause of diarrhoeal disease among infants and young children. Nearly every child in the world is infected with a rotavirus ...
protein NSP3 (NS34) is bound to the 3' end consensus sequence of viral
mRNAs in infected cells.
Four
nucleotides
Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules with ...
are the minimal requirement for RNA recognition by rotavirus
nonstructural protein In virology, a nonstructural protein is a protein encoded by a virus but that is not part of the viral particle. They typically include the various enzymes and transcription factors the virus uses to replicate itself, such as a viral protease ( 3CL ...
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
Poly(A)-binding protein (PAB or PABP) is an RNA-binding protein which triggers the binding of eukaryotic initiation factor 4 complex (eIF4G) directly to the poly(A) tail of mRNA which is 200-250 nucleotides long. The poly(A) tail is located on th ...
from
eIF4F
Eukaryotic initiation factor 4F (eIF4F) is a heterotrimeric protein complex that binds the 5' cap of messenger RNAs (mRNAs) to promote eukaryotic translation initiation. The eIF4F complex is composed of three non-identical subunits: the DEAD-b ...
. 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
Translation is the communication of the meaning of a source-language text by means of an equivalent target-language text. The English language draws a terminological distinction (which does not exist in every language) between ''transla ...
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
RoXaN (Rotavirus 'X'-associated non-structural protein) also known as ZC3H7B (zinc finger CCCH-type containing 7B), is a protein that in humans is encoded by the ''ZC3H7B'' gene. RoXaN is a protein that contains tetratricopeptide repeat and l ...
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
{{reflist, 32
Rotaviruses
RNA-binding proteins
Viral nonstructural proteins