Dynamics of the human and viral m6A RNA methylomes during HIV-1 infection of T cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE74016 | GEO | 2016/02/16
SECONDARY ACCESSION(S): PRJNA298743
REPOSITORIES: GEO
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Project description:HIV-1 exploits host cell post-translation modifications (PTMs) to facilitate production of infectious particles. These modifications include SUMOylation, a dynamically regulated PTM involving covalent attachment of small ubiquitin-like modifiers (SUMOs) to lysine (K) residues of target proteins. SUMOylation modulates the activity of thousands of proteins and multiple fundamental host cellular processes, including pathways hijacked by HIV-1 to promote infection and spread. The SUMOylation of several proteins during HIV-1 infection has been characterized. However, the broad effects of HIV-1 infection on the SUMOylation of the host cell proteome is largely unknown. To date, SUMOylation has not been explored by large-scale proteomics in the context of HIV infection, where many SUMO-regulated host dependency factors remain to be identified. In this study, we performed a proteome-wide, mass spectrometry (MS)-based screen to identify proteins that are SUMOylated during HIV-1 infection. Here, and in immunoprecipitation assays, infection with HIV-1 led to the widespread increased SUMOylation of the heterogeneous nuclear ribonucleoprotein (HNRNP) A/B proteins, a protein family central to the regulation of alternative splicing. Intriguingly, this phenotype was found to be driven by expression of the HIV-1 Viral Infectivity Factor (Vif), suggesting a novel function for this protein aside from APOBEC3G degradation. We selected HNRNPA2B1 (A2/B1) and HNRNPA3 for further study, where depletion of these proteins led to the altered splicing of HIV-1 viral RNAs and dramatically reduced HIV-1 infectivity. Considering the enrichment of SUMOylation sites within the RNA-binding domains of the HNRNPA/B family, our data suggest a novel mechanism involving HIV-1-induced, Vif-mediated SUMOylation of host RNA splicing factors as a means to regulate HIV-1 alternative splicing. Broadly, our findings suggest that infection with HIV-1 alters the SUMOylation of many unexplored host cellular proteins, and provides a significant proteomic resource for their future mechanistic study.
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