An Interaction between KSHV ORF57 and UIF Provides mRNA-Adaptor Redundancy in Herpesvirus Intronless mRNA Export

PLoS Pathogens

James R. Boyne¹  Rachel Wheat¹  Guillaume M. Hautbergue¹  David J. Blackbourn²  Stuart A. Wilson²  Brian R. Jackson³  Matthew J. Walsh³  Adam Taylor³  Marko Noerenberg³  Adrian Whitehouse⁴ 

[1] Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, United Kingdom;Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, United Kingdom;Institute of Molecular and Cellular Biology, University of Leeds, Leeds, United Kingdom;School of Cancer Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom

关键词: Messenger RNA;    Kaposi's sarcoma-associated herpesvirus;    Co-immunoprecipitation;    HEK 293 cells;    Immunoprecipitation;    Antibodies;    Ribonucleoproteins;    Recombinant protein purification;   

DOI  :  10.1371/journal.ppat.1002138

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY