title: The interaction of the cellular export adaptor protein Aly/REF with ICP27 contributes to the efficiency of herpes simplex virus 1 mRNA export.
abstract: Herpes simplex virus 1 (HSV-1) protein ICP27 enables viral mRNA export by accessing the cellular mRNA export receptor TAP/NXF, which guides mRNA through the nuclear pore complex. ICP27 binds viral mRNAs and interacts with TAP/NXF, providing a link to the cellular mRNA export pathway. ICP27 also interacts with the mRNA export adaptor protein Aly/REF, which binds cellular mRNAs and also interacts with TAP/NXF. Studies using small interfering RNA (siRNA) knockdown indicated that Aly/REF is not required for cellular mRNA export, and similar knockdown studies during HSV-1 infection led us to conclude that Aly/REF may be dispensable for viral RNA export. Recently, the structural basis of the interaction of ICP27 with Aly/REF was elucidated at atomic resolution, and it was shown that three ICP27 residues, W105, R107, and L108, interface with the RNA recognition motif (RRM) domain of Aly/REF. Here, to determine the role the interaction of ICP27 and Aly/REF plays during infection, these residues were mutated to alanine, and a recombinant virus, WRL-A, was constructed. Virus production was reduced about 10-fold during WRL-A infection, and export of ICP27 protein and most viral mRNAs was less efficient. We conclude that interaction of ICP27 with Aly/REF contributes to efficient viral mRNA export.
authors: Department of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, California, USA.
authors: Xiaochen
authors: X
authors: Tian
authors: Gayathri
authors: G
authors: Devi-Rao
authors: Alexander P
authors: AP
authors: Golovanov
authors: Rozanne M
authors: RM
authors: Sandri-Goldin
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D002522:Chlorocebus aethiops; D017931:DNA Primers / Q000235:genetics; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D018259:Herpesvirus 1, Human / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D046228:Microarray Analysis; D016296:Mutagenesis; D009687:Nuclear Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014709:Vero Cells
chemical_list: C105242:ALYREF protein, human; D017931:DNA Primers; C057120:ICP27 protein, human herpesvirus 1; D017874:Immediate-Early Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014157:Transcription Factors
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