Adenovirus infection induces HuR relocalization to facilitate virus replication

Journal Article · Mon Jan 15 04:00:00 EST 2018 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2017.12.036· OSTI ID:23134405

Jehung, Jumond P. ^[1]; Kitamura, Tetsuya; Yanagawa-Matsuda, Aya ^[2]; Kuroshima, Takeshi ^[3]; Towfik, Alam ^[4]; others, and

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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)

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.

• OSTI ID: 23134405
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 495; ISSN BBRCA9; ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ADENOVIRUS
CELL TRANSFORMATIONS
CYTOPLASM
LUCIFERASE
MESSENGER-RNA
ONCOGENES
TETRACYCLINES