The RNA chaperone AUF1 assists West Nile virus RNA replication

Previous work. Searching for cellular factors that support the intracellular replication of the RNA genome of the important human pathogen West Nile virus (WNV) we recently defined the RNA binding protein AUF1 (hnRNP D) as a new important WNV host factor. Testing of the four known AUF1 isoforms revealed that only one, p45, significantly stimulates viral RNA synthesis. Most interestingly, AUF1 p45 was shown functioning as a RNA chaperone that considerably enhances the interaction of the WNV RNA’s 5’ and 3’ termini, which is an essential prerequisite for viral replication. The efficiency of AUF1 p45-mediated RNA annealing and its stimulatory effect on viral RNA synthesis were demonstrated to depend on arginine-methylation of the protein. Aim. Our data suggest that methylated AUF1 p45 facilitates cyclization of the viral RNA genome and thus assists Flavivirus RNA replication. The project aims at further substantiating this regulatory model.