Biology subjects

Ruscica, V.

Publications and source records attributed to Ruscica, V..

3 recordsLinked to original sources

bioRxiv2024

XRN1 supplies free nucleotides to feed alphavirus replication

Several RNA viruses induce widespread degradation of cellular mRNAs upon infection; however, the biological significance and mechanistic details of this phenomenon remain unknown. Here, we make use of a model alphavirus, Sindbis virus (SINV), to fill this knowledge gap. We found that SINV triggers cellular RNA decay through the exonuclease XRN1 and the 5-to-3 degradation machinery (5-3DM). These proteins accumulate at viral replication organelles (VROs) and interact with the non-structural protein 1 (nsP1), bringing mRNA degradation into proximity with vRNA synthesis. Our data suggest that monophosphate nucleotides released by cellular RNA decay are recycled through the salvage pathway to feed viral replications. Our work thus reveals a fundamental connection between cellular mRNA degradation and viral replication via nucleotides repurposing. Research highlightsO_LI5-3 RNA decay is essential for the replication of a wide range of viruses. C_LIO_LIXRN1 directly interacts with transcripts which are degraded during infection. C_LIO_LIRNA decay factors and salvage pathway members localise to viral factories. C_LIO_LISupplying nucleosides to several 5-3DM deficient cells facilitates SINV infection. C_LI

biochemistry↗

bioRxiv2023

Incorporation of genome-bound cellular proteins into HIV-1 particles regulates viral infection

The initial steps of the human immunodeficiency virus 1 (HIV-1) lifecycle are regulated by cellular RNA-binding proteins (RBPs). To understand the scope of these early host-virus interactions, we developed in virion RNA interactome capture (ivRIC), which allowed the comprehensive and systematic profiling of the proteins that interact with the HIV-1 genomic (g)RNA inside viral particles. ivRIC identified 104 cellular RBPs within the encapsidated HIV-1 ribonucleoprotein, many of which are typically found in the cellular nucleus. Notably, these nuclear RBPs interact with the HIV-1 RBP Rev, suggesting that they associate with HIV-1 gRNA during its nuclear life. Functional assays show that ivRBPs are important for HIV-1, including PURA and PURB, which control viral gene expression and infectivity through interaction with critical sequences in the gRNA. Our characterisation of the composition of the encapsidated ribonucleoprotein of HIV-1 uncovers new host-virus interactions that invokes new mechanisms for controlling HIV-1 infection.

molecular biology↗

bioRxiv2021

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

RNA is a central molecule for RNA viruses, acting as mRNA and genome. However, the interactions that viral (v)RNA establishes with the host cell is only starting to be elucidated. Here, we determine with unprecedented depth the composition of the ribonucleoproteins (RNPs) of the prototypical arthropod-borne Sindbis virus (SINV) using viral RNA interactome capture. We show that SINV RNAs engage with hundreds of cellular proteins and pathways, including a group of nuclear RNA-binding proteins (RBPs) with unknown roles in infection. Combining subcellular fractionation and proteomics with several orthogonal approaches, we demonstrate that these nuclear RBPs are selectively redistributed to the cytoplasm after infection, where they associate with the viral replication organelles. These nuclear RBPs potently supress viral gene expression, with activities spanning viral species and families. Our study provides a comprehensive and systematic analysis of SINV RNP composition, revealing a network of nuclear RBPs with moonlighting antiviral function. Research highlightsO_LISINV RNAs interact with over four hundred cellular RBPs C_LIO_LISINV induces selective cytoplasmic translocation of a subset of nuclear RBPs C_LIO_LIThese nuclear RBPs display potent antiviral effects C_LIO_LIThe SF3B complex binds to SINV RNA and supresses infection in a splicing-independent manner C_LI

microbiology↗