Adenovirus infection induces HuR relocalization to facilitate virus replication |
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Authors: | Jumond P. Jehung Tetsuya Kitamura Aya Yanagawa-Matsuda Takeshi Kuroshima Alam Towfik Motoaki Yasuda Hidehiko Sano Yoshimasa Kitagawa Kazuyuki Minowa Masanobu Shindoh Fumihiro Higashino |
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Affiliation: | 1. Department of Restorative Dentistry, Hokkaido University, Faculty of Dental Medicine, Graduate School of Dental Medicine, Sapporo, Japan;2. Department of Oral Pathology and Biology, Hokkaido University, Faculty of Dental Medicine, Graduate School of Dental Medicine, Sapporo, Japan;3. Department of Oral Diagnosis and Medicine, Hokkaido University, Faculty of Dental Medicine, Graduate School of Dental Medicine, Sapporo, Japan;4. Department of Dental Radiology, Hokkaido University, Faculty of Dental Medicine, Graduate School of Dental Medicine, Sapporo, Japan;5. Department of Oral Molecular Microbiology, Hokkaido University, Faculty of Dental Medicine, Graduate School of Dental Medicine, Sapporo, Japan;6. Department of Molecular Oncology, Hokkaido University, Faculty of Dental Medicine, Graduate School of Biomedical Science and Engineering, Sapporo, Japan |
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Abstract: | HuR is an RNA-binding protein of the embryonic lethal abnormal vision (ELAV) family, which binds to the AU-rich element (ARE) in the 3′-untranslated region (UTR) of certain mRNAs and is involved in the nucleo-cytoplasmic export and stabilization of ARE-mRNAs. The cytoplasmic relocalization of ARE-mRNAs with several proteins such as HuR and pp32 increases in cells transformed by the adenovirus oncogene product E4orf6. Additionally, these ARE-mRNAs were stabilized and acquired the potential to transform cells. Although, the relocalization of HuR and the stabilization of ARE-mRNAs are crucial for cell transformation, evidence regarding the relationship of HuR and ARE-mRNAs with adenovirus replication is lacking. In this report, we demonstrate that adenovirus infection induces the relocation of HuR to the cytoplasm of host cells. Analysis using the luciferase-ARE fusion gene and the tetracycline (tet)-off system revealed that the process of stabilizing ARE-mRNAs is activated in adenovirus-infected cells. Heat shock treatment or knockdown-mediated depletion of HuR reduced adenovirus production. Furthermore, expression of ARE-including viral IVa2 mRNA, decreased in HuR-depleted infected cells. These results indicate that HuR plays an important role in adenovirus replication, at least in part, by up-regulating IVa2 mRNA expression and that ARE-mRNA stabilization is required for both transformation and virus replication. |
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Keywords: | Corresponding author. Department of Oral Pathology and Biology Hokkaido University Faculty of Dental Medicine Graduate School of Dental Medicine N-13 W-7 Kita-ku Sapporo 060-8586 Japan. |
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