miR-30a enhanced RIG-I-mediated type I interferon antiviral response by targeting USP14
ABSTRACT Type I interferon (IFN) signaling plays a prominent role in the host innate immune defense against viral infection. The regulatory roles of miRNAs on the innate immune response remain to be further explored. Although miR-30a has been implicated in the regulation of various viral life cycles...
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American Society for Microbiology
2025-08-01
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| Series: | Microbiology Spectrum |
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| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.00188-25 |
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| author | Jikai Zhang Yiwen Wang Ningye Sun Botao Zou Zijie Wang Hang Yin Jiaqian Xie Banruo Xia Nan Sun |
| author_facet | Jikai Zhang Yiwen Wang Ningye Sun Botao Zou Zijie Wang Hang Yin Jiaqian Xie Banruo Xia Nan Sun |
| author_sort | Jikai Zhang |
| collection | DOAJ |
| description | ABSTRACT Type I interferon (IFN) signaling plays a prominent role in the host innate immune defense against viral infection. The regulatory roles of miRNAs on the innate immune response remain to be further explored. Although miR-30a has been implicated in the regulation of various viral life cycles, the underlying mechanism on type I IFN signaling remains controversial. Herein, miR-30a was identified as a regulator of type 1 IFN production in macrophages. We observed that miR-30a expression was significantly decreased by vesicular stomatitis virus (VSV) or Sendai virus (SeV) infection in THP-1 cells. In return, overexpression of miR-30a promoted viral infection-triggered IFN and ISGs production to inhibit VSV or SeV replication. Mechanistically, miR-30a inhibited USP14 expression by binding with the 3′UTR of mRNA. USP14 was identified as an inhibitor of IFN signaling by removing the K63-linked ubiquitination from RIG-I, as previously reported. Consequently, miR-30a, by downregulating USP14 expression, enhanced the K63-linked ubiquitination of RIG-I to exert broad-spectrum antiviral effects. Overall, this study revealed a novel antiviral mechanism of miR-30a through the miR-30a-USP14-RIG-I axis and enriched miRNA–innate immunity regulatory networks.IMPORTANCEmiRNAs are involved in the regulation of innate immune responses and affect the life cycle of viruses. In this study, we identified miR-30a as a potent positive regulator of type I IFN signaling. The further mechanistic study revealed that miR-30a, by targeting and inhibiting USP14 expression, promoted RIG-I K63 ubiquitination to enhance type I IFN responses, thereby resulting in broad-spectrum antiviral effects against multiple viruses. As a complex regulatory network, the activation of type I interferon responses could subsequently reduce miR-30a expression to prevent the dysregulated activation. The insights gained could be crucial for developing innovative antiviral strategies to combat viral infections. |
| format | Article |
| id | doaj-art-1eda08b594ac47bdbfc81e12dc7e7d65 |
| institution | DOAJ |
| issn | 2165-0497 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj-art-1eda08b594ac47bdbfc81e12dc7e7d652025-08-20T02:56:43ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972025-08-0113810.1128/spectrum.00188-25miR-30a enhanced RIG-I-mediated type I interferon antiviral response by targeting USP14Jikai Zhang0Yiwen Wang1Ningye Sun2Botao Zou3Zijie Wang4Hang Yin5Jiaqian Xie6Banruo Xia7Nan Sun8Jiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, ChinaJiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, ChinaJiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, ChinaJiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, ChinaJiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou, ChinaJiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, ChinaJiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, ChinaJiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, ChinaJiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, ChinaABSTRACT Type I interferon (IFN) signaling plays a prominent role in the host innate immune defense against viral infection. The regulatory roles of miRNAs on the innate immune response remain to be further explored. Although miR-30a has been implicated in the regulation of various viral life cycles, the underlying mechanism on type I IFN signaling remains controversial. Herein, miR-30a was identified as a regulator of type 1 IFN production in macrophages. We observed that miR-30a expression was significantly decreased by vesicular stomatitis virus (VSV) or Sendai virus (SeV) infection in THP-1 cells. In return, overexpression of miR-30a promoted viral infection-triggered IFN and ISGs production to inhibit VSV or SeV replication. Mechanistically, miR-30a inhibited USP14 expression by binding with the 3′UTR of mRNA. USP14 was identified as an inhibitor of IFN signaling by removing the K63-linked ubiquitination from RIG-I, as previously reported. Consequently, miR-30a, by downregulating USP14 expression, enhanced the K63-linked ubiquitination of RIG-I to exert broad-spectrum antiviral effects. Overall, this study revealed a novel antiviral mechanism of miR-30a through the miR-30a-USP14-RIG-I axis and enriched miRNA–innate immunity regulatory networks.IMPORTANCEmiRNAs are involved in the regulation of innate immune responses and affect the life cycle of viruses. In this study, we identified miR-30a as a potent positive regulator of type I IFN signaling. The further mechanistic study revealed that miR-30a, by targeting and inhibiting USP14 expression, promoted RIG-I K63 ubiquitination to enhance type I IFN responses, thereby resulting in broad-spectrum antiviral effects against multiple viruses. As a complex regulatory network, the activation of type I interferon responses could subsequently reduce miR-30a expression to prevent the dysregulated activation. The insights gained could be crucial for developing innovative antiviral strategies to combat viral infections.https://journals.asm.org/doi/10.1128/spectrum.00188-25miR-30aRIG-IUSP14ubiquitinationinnate immunityantiviral effects |
| spellingShingle | Jikai Zhang Yiwen Wang Ningye Sun Botao Zou Zijie Wang Hang Yin Jiaqian Xie Banruo Xia Nan Sun miR-30a enhanced RIG-I-mediated type I interferon antiviral response by targeting USP14 Microbiology Spectrum miR-30a RIG-I USP14 ubiquitination innate immunity antiviral effects |
| title | miR-30a enhanced RIG-I-mediated type I interferon antiviral response by targeting USP14 |
| title_full | miR-30a enhanced RIG-I-mediated type I interferon antiviral response by targeting USP14 |
| title_fullStr | miR-30a enhanced RIG-I-mediated type I interferon antiviral response by targeting USP14 |
| title_full_unstemmed | miR-30a enhanced RIG-I-mediated type I interferon antiviral response by targeting USP14 |
| title_short | miR-30a enhanced RIG-I-mediated type I interferon antiviral response by targeting USP14 |
| title_sort | mir 30a enhanced rig i mediated type i interferon antiviral response by targeting usp14 |
| topic | miR-30a RIG-I USP14 ubiquitination innate immunity antiviral effects |
| url | https://journals.asm.org/doi/10.1128/spectrum.00188-25 |
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