Compositional analysis of Sindbis virus ribonucleoproteins reveals an extensive co-opting of key nuclear RNA-binding proteins (preprint)

The expansion of tropical mosquito habitats and associated arboviruses is a risk for human health, and it thus becomes fundamental to identify new antiviral strategies. In this study we employ a new approach to elucidate the composition of the ribonucleoproteins (RNPs) of a prototypical arbovirus called Sindbis (SINV). SINV RNPs contain 453 cellular and 6 viral proteins, many of these proteins are nuclear in uninfected cells and redistribute to the cytoplasm upon infection. These findings suggest that SINV RNAs act as spiderwebs, capturing host factors required for viral replication and gene expression in the cytoplasm. Functional perturbation of several of these host proteins causes profound effects in virus infection, as illustrated here with the tRNA ligase complex. Moreover, inhibition of viral RNP components with available drugs hampers the infection of a wide range of viruses, opening new avenues for the development of broad-spectrum therapies. Research highlightsO_LISINV RNA interactome includes 453 cellular and 6 viral proteins. C_LIO_LINuclear RBPs that interact with SINV RNA are selectively redistributed to the cytoplasm upon infection C_LIO_LIThe tRNA ligase complex plays major regulatory roles in SINV and SARS-CoV- 2 replication C_LIO_LIThe SINV RNA interactome is enriched in pan-viral regulators with therapeutic potential. C_LI

Global analysis of protein-RNA interactions in SARS-CoV-2 infected cells reveals key regulators of infection (preprint)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19. SARS-CoV-2 relies on cellular RNA-binding proteins (RBPs) to replicate and spread, although which RBPs control SARS-CoV-2 infection remains largely unknown. Here, we employ a multi-omic approach to identify systematically and comprehensively which cellular and viral RBPs are involved in SARS-CoV-2 infection. We reveal that the cellular RNA-bound proteome is remodelled upon SARS-CoV-2 infection, having widespread effects on RNA metabolic pathways, non-canonical RBPs and antiviral factors. Moreover, we apply a new method to identify the proteins that directly interact with viral RNA, uncovering dozens of cellular RBPs and six viral proteins. Amongst them, several components of the tRNA ligase complex, which we show regulate SARS-CoV-2 infection. Furthermore, we discover that available drugs targeting host RBPs that interact with SARS-CoV-2 RNA inhibit infection. Collectively, our results uncover a new universe of host-virus interactions with potential for new antiviral therapies against COVID-19.