System-wide profiling of protein-RNA interactions in sindbis infected cells reveals host regulators of infection

RNA viruses rely on cellular RNA-binding proteins (RBPs) to infect the host cell. However, the repertoire of the cellular RBPs exploited by viruses is largely unknown. Using the ‘RNA interactome capture’ method, we profiled in a proteome-wide scale the RBP-RNA interactions occurring during sindbis virus (SINV) infection. We discover that SINV affects the activity of hundreds of RBPs, essentially rewiring the host RNA-bound proteome. Such alterations do not relate to changes in protein abundance but are rather due to subcellular redistribution of RBPs and pervasive transcriptome remodelling. Strikingly, RBPs stimulated by SINV accumulate in the cytoplasmic compartments where the virus replicates and interact with viral RNA. Perturbation of these RBPs can restrict or promote infection; for example, GEMIN5 binds to key regulatory regions of SINV RNAs and inhibits viral protein expression. Importantly, we show that drug based RBP intervention may have potential as therapeutic strategy against viruses.