Kaposi's sarcoma-associated herpesvirus ORF57 protein interacts with PYM to enhance translation of viral intronless mRNAs

James R. Boyne, Brian R. Jackson, Adam Taylor, Stuart A. MacNab, Adrian Whitehouse

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) expresses numerous intronless mRNAs that are unable to access splicing-dependent cellular mRNA nuclear export pathways. To circumvent this problem, KSHV encodes the open reading frame 57 (ORF57) protein, which orchestrates the formation of an export-competent virus ribonucleoprotein particle comprising the nuclear export complex hTREX, but not the exon-junction complex (EJC). Interestingly, EJCs stimulate mRNA translation, which raises the intriguing question of how intronless KSHV transcripts are efficiently translated. Herein, we show that ORF57 associates with components of the 48S pre-initiation complex and co-sediments with the 40S ribosomal subunits. Strikingly, we observed a direct interaction between ORF57 and PYM, a cellular protein that enhances translation by recruiting the 48S pre-initiation complex to newly exported mRNAs, through an interaction with the EJC. Moreover, detailed biochemical analysis suggests that ORF57 recruits PYM to intronless KSHV mRNA and PYM then facilitates the association of ORF57 and the cellular translation machinery. We, therefore, propose a model whereby ORF57 interacts directly with PYM to enhance translation of intronless KSHV transcripts.

Original languageEnglish
Pages (from-to)1851-1864
Number of pages14
JournalEMBO Journal
Volume29
Issue number11
DOIs
Publication statusPublished - 2 Jun 2010
Externally publishedYes

Fingerprint

Human Herpesvirus 8
Open Reading Frames
Messenger RNA
Proteins
Cell Nucleus Active Transport
Protein Biosynthesis
Exons
Eukaryotic Small Ribosome Subunits
Ribonucleoproteins
Viruses
Machinery
Sediments
Virion

Cite this

Boyne, James R. ; Jackson, Brian R. ; Taylor, Adam ; MacNab, Stuart A. ; Whitehouse, Adrian. / Kaposi's sarcoma-associated herpesvirus ORF57 protein interacts with PYM to enhance translation of viral intronless mRNAs. In: EMBO Journal. 2010 ; Vol. 29, No. 11. pp. 1851-1864.
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Kaposi's sarcoma-associated herpesvirus ORF57 protein interacts with PYM to enhance translation of viral intronless mRNAs. / Boyne, James R.; Jackson, Brian R.; Taylor, Adam; MacNab, Stuart A.; Whitehouse, Adrian.

In: EMBO Journal, Vol. 29, No. 11, 02.06.2010, p. 1851-1864.

Research output: Contribution to journalArticle

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AB - Kaposi's sarcoma-associated herpesvirus (KSHV) expresses numerous intronless mRNAs that are unable to access splicing-dependent cellular mRNA nuclear export pathways. To circumvent this problem, KSHV encodes the open reading frame 57 (ORF57) protein, which orchestrates the formation of an export-competent virus ribonucleoprotein particle comprising the nuclear export complex hTREX, but not the exon-junction complex (EJC). Interestingly, EJCs stimulate mRNA translation, which raises the intriguing question of how intronless KSHV transcripts are efficiently translated. Herein, we show that ORF57 associates with components of the 48S pre-initiation complex and co-sediments with the 40S ribosomal subunits. Strikingly, we observed a direct interaction between ORF57 and PYM, a cellular protein that enhances translation by recruiting the 48S pre-initiation complex to newly exported mRNAs, through an interaction with the EJC. Moreover, detailed biochemical analysis suggests that ORF57 recruits PYM to intronless KSHV mRNA and PYM then facilitates the association of ORF57 and the cellular translation machinery. We, therefore, propose a model whereby ORF57 interacts directly with PYM to enhance translation of intronless KSHV transcripts.

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