Uncoupling of hTREX demonstrates that UAP56 and hTHO-complex recruitment onto herpesvirus saimiri intronless transcripts is required for replication

1 Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK 2 Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK Correspondence Adrian Whitehouse a.whitehouse{at}leeds.ac.uk Herpesvirus saimiri (HVS) ORF57 nucleocytoplasmic shuttle protein binds viral RNA and interacts with the cellular nuclear export adaptor protein, Aly, to access the TAP-mediated nuclear export pathway. This enables the efficient nuclear export of HVS intronless mRNAs. Herein, we extend these studies and demonstrate that ORF57 recruits several members of hTREX, namely Aly, UAP56 and hTHO-complex proteins, onto the viral mRNAs to assemble an export-competent ribonucleoprotein particle. Moreover, using a transdominant form of Aly which inhibits UAP56 and hTHO-complex association with viral intronless mRNA, we show that complete hTREX recruitment is required for efficient HVS mRNA nuclear export and replication. These authors contributed equally to this work. Two supplementary figures are available with the online version of this paper.