An interaction between KSHV ORF57 and UIF provides mRNA-adaptor redundancy in herpesvirus intronless mRNA export

The hTREX complex mediates cellular bulk mRNA nuclear export by recruiting the nuclear export factor, TAP, via a direct interaction with the export adaptor, Aly. Intriguingly however, depletion of Aly only leads to a modest reduction in cellular mRNA nuclear export, suggesting the existence of addit...

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Veröffentlicht in:PLoS pathogens 2011-07, Vol.7 (7), p.e1002138-e1002138
Hauptverfasser: Jackson, Brian R, Boyne, James R, Noerenberg, Marko, Taylor, Adam, Hautbergue, Guillaume M, Walsh, Matthew J, Wheat, Rachel, Blackbourn, David J, Wilson, Stuart A, Whitehouse, Adrian
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container_end_page e1002138
container_issue 7
container_start_page e1002138
container_title PLoS pathogens
container_volume 7
creator Jackson, Brian R
Boyne, James R
Noerenberg, Marko
Taylor, Adam
Hautbergue, Guillaume M
Walsh, Matthew J
Wheat, Rachel
Blackbourn, David J
Wilson, Stuart A
Whitehouse, Adrian
description The hTREX complex mediates cellular bulk mRNA nuclear export by recruiting the nuclear export factor, TAP, via a direct interaction with the export adaptor, Aly. Intriguingly however, depletion of Aly only leads to a modest reduction in cellular mRNA nuclear export, suggesting the existence of additional mRNA nuclear export adaptor proteins. In order to efficiently export Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs from the nucleus, the KSHV ORF57 protein recruits hTREX onto viral intronless mRNAs allowing access to the TAP-mediated export pathway. Similarly however, depletion of Aly only leads to a modest reduction in the nuclear export of KSHV intronless mRNAs. Herein, we identify a novel interaction between ORF57 and the cellular protein, UIF. We provide the first evidence that the ORF57-UIF interaction enables the recruitment of hTREX and TAP to KSHV intronless mRNAs in Aly-depleted cells. Strikingly, depletion of both Aly and UIF inhibits the formation of an ORF57-mediated nuclear export competent ribonucleoprotein particle and consequently prevents ORF57-mediated mRNA nuclear export and KSHV protein production. Importantly, these findings highlight that redundancy exists in the eukaryotic system for certain hTREX components involved in the mRNA nuclear export of intronless KSHV mRNAs.
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Intriguingly however, depletion of Aly only leads to a modest reduction in cellular mRNA nuclear export, suggesting the existence of additional mRNA nuclear export adaptor proteins. In order to efficiently export Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs from the nucleus, the KSHV ORF57 protein recruits hTREX onto viral intronless mRNAs allowing access to the TAP-mediated export pathway. Similarly however, depletion of Aly only leads to a modest reduction in the nuclear export of KSHV intronless mRNAs. Herein, we identify a novel interaction between ORF57 and the cellular protein, UIF. We provide the first evidence that the ORF57-UIF interaction enables the recruitment of hTREX and TAP to KSHV intronless mRNAs in Aly-depleted cells. Strikingly, depletion of both Aly and UIF inhibits the formation of an ORF57-mediated nuclear export competent ribonucleoprotein particle and consequently prevents ORF57-mediated mRNA nuclear export and KSHV protein production. Importantly, these findings highlight that redundancy exists in the eukaryotic system for certain hTREX components involved in the mRNA nuclear export of intronless KSHV mRNAs.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>21814512</pmid><doi>10.1371/journal.ppat.1002138</doi><oa>free_for_read</oa></addata></record>
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subjects Active Transport, Cell Nucleus - genetics
Biology
Cell Nucleus - genetics
Cell Nucleus - metabolism
Cell Nucleus - virology
Colleges & universities
Competition
Experiments
Gene expression
Genetic aspects
Genetics
HEK293 Cells
Herpesvirus 8, Human - genetics
Herpesvirus 8, Human - metabolism
Herpesviruses
Humans
Messenger RNA
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
Properties
Proteins
Recruitment
RNA, Messenger - genetics
RNA, Messenger - metabolism
RNA, Viral - genetics
RNA, Viral - metabolism
RNA-Binding Proteins - genetics
RNA-Binding Proteins - metabolism
Viral Proteins - genetics
Viral Proteins - metabolism
title An interaction between KSHV ORF57 and UIF provides mRNA-adaptor redundancy in herpesvirus intronless mRNA export
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