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

Jackson, B. R., Boyne, J. R., Noerenberg, M. , Taylor, A., Hautbergue, G. M., Walsh, M. J., Wheat, R., Blackbourn, D. J., Wilson, S. A. and Whitehouse, A. (2011) An interaction between KSHV ORF57 and UIF provides mRNA-adaptor redundancy in herpesvirus intronless mRNA export. PLoS Pathogens, 7(7), e1002138. (doi: 10.1371/journal.ppat.1002138) (PMID:21814512) (PMCID:PMC3141038)

Abstract

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.

• Item Type: Articles
• Additional Information: This work was supported in part by project grants from the Wellcome Trust (086168), BBSRC (BB/G022836/1 and BB/F012101/1) and Cancer Research UK (CRUKDJD1).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Noerenberg, Dr Marko
• Authors: Jackson, B. R., Boyne, J. R., Noerenberg, M., Taylor, A., Hautbergue, G. M., Walsh, M. J., Wheat, R., Blackbourn, D. J., Wilson, S. A., and Whitehouse, A.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: PLoS Pathogens
• Publisher: Public Library of Science
• ISSN: 1553-7366
• ISSN (Online): 1553-7374
• Published Online: 21 July 2011
• Copyright Holders: Copyright © 2011 Jackson et al.
• First Published: First published in PLoS Pathogens 7(7): e1002138
• Publisher Policy: Reproduced under a Creative Commons License