文章基本信息

标题：Overlapping motifs on the herpes viral proteins ICP27 and ORF57 mediate interactions with the mRNA export adaptors ALYREF and UIF
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作者：Richard B. Tunnicliffe ; Xiaochen Tian ; Joanna Storer 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2018
卷号：8
期号：1
页码：15005
DOI：10.1038/s41598-018-33379-x
语种：English
出版社：Springer Nature
摘要：The TREX complex mediates the passage of bulk cellular mRNA export to the nuclear export factor TAP/NXF1 via the export adaptors ALYREF or UIF, which appear to act in a redundant manner. TREX complex recruitment to nascent RNA is coupled with 5' capping, splicing and polyadenylation. Therefore to facilitate expression from their intronless genes, herpes viruses have evolved a mechanism to circumvent these cellular controls. Central to this process is a protein from the conserved ICP27 family, which binds viral transcripts and cellular TREX complex components including ALYREF. Here we have identified a novel interaction between HSV-1 ICP27 and an N-terminal domain of UIF in vivo, and used NMR spectroscopy to locate the UIF binding site within an intrinsically disordered region of ICP27. We also characterized the interaction sites of the ICP27 homolog ORF57 from KSHV with UIF and ALYREF using NMR, revealing previously unidentified binding motifs. In both ORF57 and ICP27 the interaction sites for ALYREF and UIF partially overlap, suggestive of mutually exclusive binding. The data provide a map of the binding sites responsible for promoting herpes virus mRNA export, enabling future studies to accurately probe these interactions and reveal the functional consequences for UIF and ALYREF redundancy.