Promiscuous RNA Binding Ensures Effective Encapsidation of APOBEC3 Proteins by HIV-1

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APOBEC3 proteins are cell-encoded restriction factors that counteract infections, particularly by retroviruses such as HIV-1, and retrotransposons. When packaged into HIV-1 particles, APOBEC3G and APOBEC3F both inhibit reverse transcription and induce destructive hypermutation in viral DNA. The mechanism of APOBEC3 virion packaging awaits elucidation, though a dependency on RNA binding has been established. Here, we employed a cross-linking and next generation sequencing approach to determine which RNAs are bound to A3G and A3F in HIV-1 infected cells. We show that both proteins bind to multiple different RNAs, including viral RNA as well as cellular coding and non-coding RNAs, with relatively little evidence of selectivity. We then developed a complementation assay to address the diversity of RNAs that can act as substrates for A3G/F virion packaging. Consistent with the RNA binding profiles, many RNAs can promote packaging provided that those RNAs are, themselves, packaged. These observations suggest that APOBEC3 packaging lacks selectivity and is driven simply by the non-specific RNA binding capabilities of these proteins. We speculate that this model accounts for the broad range of retro-elements that are susceptible to repression by individual APOBEC3 proteins, and also that such substrates cannot escape APOBEC3-mediated inhibition through sequence variation.

Vyšlo v časopise: Promiscuous RNA Binding Ensures Effective Encapsidation of APOBEC3 Proteins by HIV-1. PLoS Pathog 11(1): e32767. doi:10.1371/journal.ppat.1004609
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004609

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