Adenovirus-mediated ubiquitination alters protein-RNA binding and aids viral RNA processing
| Autor: | Richard Lauman, Alexander M. Price, Caitlin E. Purman, Joseph M Dybas, Eui Tae Kim, Katharina E. Hayer, Matthew D. Weitzman, Benjamin A. Garcia, Jennifer C. Liddle, Matthew Charman, Christin Herrmann |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Microbiology (medical)
Gene Expression Regulation Viral Proteomics Proteome viruses Adenoviridae Infections RNA Splicing Immunology Biology Applied Microbiology and Biotechnology Microbiology ubiquitin ligase Virus Article Adenoviridae 03 medical and health sciences Ubiquitin Genetics Protein biosynthesis Adenovirus Humans Nucleotide Motifs RNA Processing Post-Transcriptional 030304 developmental biology 0303 health sciences Gene knockdown Binding Sites Base Sequence 030306 microbiology Ubiquitination RNA Computational Biology RNA-Binding Proteins Cell Biology Cell biology Proteasome RNA processing Ubiquitin ligase complex RNA splicing Host-Pathogen Interactions biology.protein RNA Viral Protein Binding |
| Zdroj: | Nature microbiology |
| ISSN: | 2058-5276 |
| Popis: | 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. Adenovirus produces two early proteins, E1B55K and E4orf6, that become components of the host cell ubiquitin ligase complex comprising elongin-B and C, cullin-5 and RBX1. The authors identified new protein substrates that are ubiquitinated by the E1B55K–E4orf6 complex and find that hnRNP-C and RALY play an inhibitory role on late viral RNA transcripts and that this is counteracted by ubiquitination due to a reduction on the capacity of these proteins to interact with viral RNA. |
| Databáze: | OpenAIRE |
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