HuR keeps interferon-β mRNA stable.

نویسنده

  • Osamu Takeuchi
چکیده

The expression of interferon (IFN) β is highly induced in immune and nonimmune cells in response to virus infection. This upregulation is mediated at both transcriptional and posttranscriptional levels. Whereas the signaling pathways triggered by innate virus receptors leading to transcription factor activation have been extensively studied, the mechanisms by which IFN-β mRNA stability is posttranscriptionally controlled are not fully understood. In this issue of the European Journal of Immunology, Herdy et al. [Eur. J. Immunol. 2015 45:1500-1511] show that a human RNA-binding protein, embryonic lethal, abnormal vision, drosophila-like 1 (ELAVL1)/Hu antigen R (HuR), strongly associates with IFN-β mRNA via AU-rich sequences present in its 3' untranslated region in various human cell lines. The authors show that ELAVL1/HuR is required for the stabilization of IFN-β mRNA, and suppression of ELAVL1/HuR by its inhibitor MS-444 leads to impaired expression of IFN-β in response to viral dsRNA treatment. Thus, this study uncovers a novel mechanism of posttranscriptional IFN-β mRNA regulation in response to virus infection, through IFN-β stabilization by ELAVL1/HuR. Future studies are expected to identify further regulatory mechanisms of IFN-β stabilization and destabilization in the course of antiviral responses.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Downregulation of β-Adrenoceptors in Isoproterenol-Induced Cardiac Remodeling through HuR

β-adrenergic receptors (β-ARs) play an important role in cardiac remodeling, which is the key pathological process in various heart diseases and leads to heart failure. However, the regulation of β-AR expression in remodeling hearts is still unclear. This study aims to clarify the possible mechanisms underlying the regulation of β1- and β2-AR expression in cardiac remodeling. The rat model of c...

متن کامل

DHA induces apoptosis and differentiation in human melanoma cells in vitro: involvement of HuR-mediated COX-2 mRNA stabilization and β-catenin nuclear translocation.

The pro-inflammatory phenotype accompanying melanoma progression includes an enhanced expression of cyclooxygenase-2 (COX-2), which plays an important role in the acquisition of apoptosis resistance, and is a suitable target for melanoma prevention and therapy. We observed that the WM266-4 metastatic melanoma cell line showed a constitutive COX-2 expression higher than that of the primary WM115...

متن کامل

NF-kappa B-mediated MyoD decay during muscle wasting requires nitric oxide synthase mRNA stabilization, HuR protein, and nitric oxide release.

Muscle wasting (cachexia) is a consequence of chronic diseases, such as cancer, and is associated with degradation of muscle proteins such as MyoD. The cytokines tumor necrosis factor alpha and gamma interferon induce muscle degeneration by activating the transcription factor NF-kappaB and its target genes. Here, we show that a downstream target of NF-kappaB is the nitric oxide (NO) synthase ge...

متن کامل

LFA-1-dependent HuR nuclear export and cytokine mRNA stabilization in T cell activation.

Lymphokine gene expression is a precisely regulated process in T cell-mediated immune responses. In this study we demonstrate that engagement of the beta(2) integrin LFA-1 in human peripheral T cells markedly extends the half-life of TNF-alpha, GM-CSF, and IL-3 mRNA, as well as a chimeric beta-globin mRNA reporter construct containing a strongly destabilizing class II AU-rich element from the G...

متن کامل

Modulation of TNF-α mRNA stability by human antigen R and miR181s in sepsis-induced immunoparalysis

Immunoparalysis is an important pathological mechanism in sepsis. However, an effective small molecule therapy is lacking. Here, we show that ouabain, a Na(+),K(+)-ATPase ligand, can reverse immunoparalysis in vitro, in vivo, and in clinical samples. Notably, the effect of ouabain was critically dependent on TNF-α expression. However, ouabain had opposing effects on the stability of TNF-α mRNA:...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • European journal of immunology

دوره 45 5  شماره 

صفحات  -

تاریخ انتشار 2015