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Adenovirus-mediated ubiquitination alters protein-RNA binding and aids viral RNA processing.

ABSTRACT: Viruses promote infection by hijacking the ubiquitin machinery of the host to counteract or redirect cellular processes. Adenovirus encodes two early proteins, E1B55K and E4orf6, that together co-opt a cellular ubiquitin ligase complex to overcome host defences and promote virus production. Adenovirus mutants lacking E1B55K or E4orf6 display defects in viral RNA processing and protein production, but previously identified substrates of the redirected ligase do not explain these phenotypes. Here, we used a quantitative proteomics approach to identify substrates of E1B55K/E4orf6-mediated ubiquitination that facilitate RNA processing. While all currently known cellular substrates of E1B55K and E4orf6 are degraded by the proteasome, we uncovered RNA-binding proteins as high-confidence substrates that are not decreased in overall abundance. We focused on two RNA-binding proteins, RALY and hnRNP-C, which we confirm are ubiquitinated without degradation. Knockdown of RALY and hnRNP-C increased levels of viral RNA splicing, protein abundance and progeny production during infection with E1B55K-deleted virus. Furthermore, infection with E1B55K-deleted virus resulted in an increased interaction of hnRNP-C with viral RNA and attenuation of viral RNA processing. These data suggest that viral-mediated ubiquitination of RALY and hnRNP-C relieves a restriction on viral RNA processing and reveal an unexpected role for non-degradative ubiquitination in the manipulation of cellular processes during virus infection.

SUBMITTER: Herrmann C

PROVIDER: S-EPMC7529849 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Adenovirus-mediated ubiquitination alters protein-RNA binding and aids viral RNA processing.

Herrmann Christin C Dybas Joseph M JM Liddle Jennifer C JC Price Alexander M AM Hayer Katharina E KE Lauman Richard R Purman Caitlin E CE Charman Matthew M Kim Eui Tae ET Garcia Benjamin A BA Weitzman Matthew D MD

Nature microbiology 20200713 10

Viruses promote infection by hijacking the ubiquitin machinery of the host to counteract or redirect cellular processes. Adenovirus encodes two early proteins, E1B55K and E4orf6, that together co-opt a cellular ubiquitin ligase complex to overcome host defences and promote virus production. Adenovirus mutants lacking E1B55K or E4orf6 display defects in viral RNA processing and protein production, but previously identified substrates of the redirected ligase do not explain these phenotypes. Here, ...[more]

PMID: 32661314

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Adenovirus-mediated ubiquitination alters protein-RNA binding and aids viral RNA processing.

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Adenovirus-mediated ubiquitination alters protein-RNA binding and aids viral RNA processing.

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