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Multiple nuclear-replicating viruses require the stress-induced protein ZC3H11A for efficient growth
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
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Number of Authors: 102018 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 115, no 16, p. e3808-E3816Article in journal (Refereed) Published
Abstract [en]

The zinc finger CCCH-type containing 11A (ZC3H11A) gene encodes a well-conserved zinc finger protein that may function in mRNA export as it has been shown to associate with the transcription export (TREX) complex in proteomic screens. Here, we report that ZC3H11A is a stress-induced nuclear protein with RNA-binding capacity that localizes to nuclear splicing speckles. During an adenovirus infection, the ZC3H11A protein and splicing factor SRSF2 relocalize to nuclear regions where viral DNA replication and transcription take place. Knockout (KO) of ZC3H11A in HeLa cells demonstrated that several nuclear-replicating viruses are dependent on ZC3H11A for efficient growth (HIV, influenza virus, herpes simplex virus, and adenovirus), whereas cytoplasmic replicating viruses are not (vaccinia virus and Semliki Forest virus). High-throughput sequencing of ZC3H11A-cross-linked RNA showed that ZC3H11A binds to short purine-rich ribonucleotide stretches in cellular and adenoviral transcripts. We show that the RNA-binding property of ZC3H11A is crucial for its function and localization. In ZC3H11A KO cells, the adenovirus fiber mRNA accumulates in the cell nucleus. Our results suggest that ZC3H11A is important for maintaining nuclear export of mRNAs during stress and that several nuclear-replicating viruses take advantage of this mechanism to facilitate their replication.

Place, publisher, year, edition, pages
2018. Vol. 115, no 16, p. e3808-E3816
Keywords [en]
ZC3H11A, mRNA export, stress response, virus infection
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:su:diva-155892DOI: 10.1073/pnas.1722333115ISI: 000430191900026PubMedID: 29610341OAI: oai:DiVA.org:su-155892DiVA, id: diva2:1202951
Available from: 2018-05-02 Created: 2018-05-02 Last updated: 2018-05-02Bibliographically approved

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