Cell Reports
Volume 23, Issue 5, 1 May 2018, Pages 1249-1258
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ZNF598 Plays Distinct Roles in Interferon-Stimulated Gene Expression and Poxvirus Protein Synthesis

https://doi.org/10.1016/j.celrep.2018.03.132Get rights and content
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Highlights

  • ZNF598 negatively regulates interferon-stimulated gene (ISG) expression

  • ZNF598 specifically functions in poxvirus infection of cell lines lacking ISG responses

  • Poxvirus protein synthesis requires ZNF598 ubiquitin ligase activity

  • Poxvirus replication requires ubiquitination of the ZNF598 substrate, RPS20

Summary

Post-translational modification of ribosomal subunit proteins (RPs) is emerging as an important means of regulating gene expression. Recently, regulatory ubiquitination of small RPs RPS10 and RPS20 by the ubiquitin ligase ZNF598 was found to function in ribosome sensing and stalling on internally polyadenylated mRNAs during ribosome quality control (RQC). Here, we reveal that ZNF598 and RPS10 negatively regulate interferon-stimulated gene (ISG) expression in primary cells, depletion of which induced ISG expression and a broad antiviral state. However, cell lines lacking interferon responses revealed that ZNF598 E3 ligase activity and ubiquitination of RPS20, but not RPS10, were specifically required for poxvirus replication and synthesis of poxvirus proteins whose encoding mRNAs contain unusual 5′ poly(A) leaders. Our findings reveal distinct functions for ZNF598 and its downstream RPS targets, one that negatively regulates ISG expression and infection by a range of viruses while the other is positively exploited by poxviruses.

Keywords

ZNF598
ubiquitination
ribosome
RPS
post-translational modification
specialization
translation
virus
poxvirus

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