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

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 expor...

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Published in:The EMBO journal 2010-06, Vol.29 (11), p.1851-1864
Main Authors: Boyne, James R, Jackson, Brian R, Taylor, Adam, Macnab, Stuart A, Whitehouse, Adrian
Format: Article
Language:English
Subjects:
Active Transport, Cell Nucleus - genetics
Biochemical analysis
Carrier Proteins - genetics
Carrier Proteins - metabolism
Cytoplasm - genetics
Cytoplasm - metabolism
EMBO23
EMBO36
Exons
Herpes viruses
Herpesvirus 8, Human - genetics
Herpesvirus 8, Human - metabolism
Human herpesvirus 8
Humans
Kaposi's sarcoma-associated herpesvirus
Kaposis sarcoma
KSHV
Molecular biology
mRNA export
Open Reading Frames - physiology
Proteins
Ribonucleic acid
Ribosomes - genetics
Ribosomes - metabolism
RNA
RNA Splicing
RNA Transport - genetics
RNA, Messenger - genetics
RNA, Messenger - metabolism
Sarcoma
translation
Virion - genetics
Virion - metabolism
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description 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.
doi_str_mv 10.1038/emboj.2010.77
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subjects Active Transport, Cell Nucleus - genetics
Biochemical analysis
Carrier Proteins - genetics
Carrier Proteins - metabolism
Cytoplasm - genetics
Cytoplasm - metabolism
EMBO23
EMBO36
Exons
Herpes viruses
Herpesvirus 8, Human - genetics
Herpesvirus 8, Human - metabolism
Human herpesvirus 8
Humans
Kaposi's sarcoma-associated herpesvirus
Kaposis sarcoma
KSHV
Molecular biology
mRNA export
Open Reading Frames - physiology
Proteins
Ribonucleic acid
Ribosomes - genetics
Ribosomes - metabolism
RNA
RNA Splicing
RNA Transport - genetics
RNA, Messenger - genetics
RNA, Messenger - metabolism
Sarcoma
translation
Virion - genetics
Virion - metabolism
title Kaposi's sarcoma-associated herpesvirus ORF57 protein interacts with PYM to enhance translation of viral intronless mRNAs
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