HuR keeps interferon-β mRNA stable.

Abstract

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.