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Nature. 2017 Jun 29;546(7660):651-655. doi: 10.1038/nature22814. Epub 2017 Jun 21.

Trans-kingdom mimicry underlies ribosome customization by a poxvirus kinase.

Author information

1
Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
2
The RNA Institute, Department of Biological Sciences, University at Albany-SUNY, Albany, New York 12222, USA.
3
Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
4
Department of Microbiology &Immunology, Stanford University School of Medicine, Stanford, California 94305, USA.

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.

PMID:
28636603
PMCID:
PMC5526112
DOI:
10.1038/nature22814
[Indexed for MEDLINE]
Free PMC Article

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