Heterogeneous nuclear ribonucleoprotein A1 regulates RNA synthesis of a cytoplasmic virus

Heterogeneous nuclear ribonucleoprotein (hnRNP A1) is involved in pre-mRNA splicing in the nucleus and translational regulation in the cytoplasm, In t he present study, we demonstrate that hnRNP A1 also participates in the tra nscription and replication of a cytoplasmic RNA virus, mouse hepatitis viru s (MHV), Overexpression of hnRNP A1 accelerated the kinetics of viral RNA s ynthesis, whereas the expression in the cytoplasm of a dominant-negative hn RNP A1 mutant that lacks the nuclear transport domain significantly delayed it, The hnRNP A1 mutant caused a global inhibition of viral mRNA transcrip tion and genomic replication, and also a preferential inhibition of the rep lication of defective-interfering RNAs. Similar to the wild-type hnRNP A1, the hnRNP A1 mutant complexed with an MHV polymerase gene product, the nucl eocapsid protein and the viral RNA. However, in contrast to the wild-type h nRNP A1, the mutant protein failed to bind a 250 kDa cellular protein, sugg esting that the recruitment of cellular proteins by hnRNP A1 is important f or MHV RNA synthesis. Our findings establish the importance of cellular fac tors in viral RNA-dependent RNA synthesis.