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Kaposi's sarcoma‐associated herpesvirus ORF57 protein interacts with PYM to enhance translation of viral intronless mRNAs
Author(s) -
Boyne James R,
Jackson Brian R,
Taylor Adam,
Macnab Stuart A,
Whitehouse Adrian
Publication year - 2010
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2010.77
Subject(s) - biology , translation (biology) , virology , genetics , messenger rna , gene
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.