Trans-kingdom mimicry underlies ribosome customization by a poxvirus kinase

Sujata Jha, Madeline G. Rollins, Gabriele Fuchs, Dean J. Procter, Elizabeth A. Hall, Kira Cozzolino, Peter Sarnow, Jeffrey N. Savas, Derek Walsh*

*Corresponding author for this work

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Ribosomes have the capacity to selectively control translation through changes in their composition that enable recognition of specific RNA elements. However, beyond differential subunit expression during development, evidence for regulated ribosome specification within individual cells has remained elusive. Here we report that a poxvirus kinase phosphorylates serine/threonine residues in the human small ribosomal subunit protein, receptor for activated C kinase (RACK1), that are not phosphorylated in uninfected cells or cells infected by other viruses. These modified residues cluster in an extended loop in RACK1, phosphorylation of which selects for translation of viral or reporter mRNAs with 5′ untranslated regions that contain adenosine repeats, so-called polyA-leaders. Structural and phylogenetic analyses revealed that although RACK1 is highly conserved, this loop is variable and contains negatively charged amino acids in plants, in which these leaders act as translational enhancers. Phosphomimetics and inter-species chimaeras have shown that negative charge in the RACK1 loop dictates ribosome selectivity towards viral RNAs. By converting human RACK1 to a charged, plant-like state, poxviruses remodel host ribosomes so that adenosine repeats erroneously generated by slippage of the viral RNA polymerase confer a translational advantage. Our findings provide insight into ribosome customization through trans-kingdom mimicry and the mechanics of species-specific leader activity that underlie poxvirus polyA-leaders.

Original languageEnglish (US)
Pages (from-to)651-655
Number of pages5
JournalNature
Volume546
Issue number7660
DOIs
StatePublished - Jun 29 2017

ASJC Scopus subject areas

  • General

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    Jha, S., Rollins, M. G., Fuchs, G., Procter, D. J., Hall, E. A., Cozzolino, K., Sarnow, P., Savas, J. N., & Walsh, D. (2017). Trans-kingdom mimicry underlies ribosome customization by a poxvirus kinase. Nature, 546(7660), 651-655. https://doi.org/10.1038/nature22814