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A host lncRNA regulates the innate immune response to an RNA virus

Cellular & Molecular Immunology volume 16, pages 841–842 (2019)Cite this article

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Recent studies have shown that more than 70% of the mammalian genome is transcribed into RNAs; however, most of these RNAs do not encode proteins and are thus called noncoding RNAs (ncRNAs). In a study published in Nature Immunology, Lin et al. reported the discovery of a new long noncoding RNA (lncRNA), Lnczc3h7a, that promotes the tripartite motif (TRIM25)-mediated K63-linked ubiquitination of retinoic acid-inducible gene-I (RIG-I), in turn augmenting downstream signal transduction.1 The authors showed that Lnczc3h7a binds to the C-terminal domain (CTD) of TRIM25 at steady state. In addition, after RIG-I recognizes pathogenic RNA, activated RIG-I is quickly recruited to form a complex with TRIM25 that serves as a molecular scaffold. This paper presents another component by which innate immunity is controlled and also provides new insight into lncRNA biology.

Lin et al. found a novel lncRNA named Lnczc3h7a among lncRNAs that coprecipitated with TRIM25 in murine macrophage RAW264.7 cells before and after RNA virus infection. Lnczc3h7a was shown to bind to the C-terminal SPRY domain of TRIM25, to which the CARD domain of activated RIG-I also binds. While the expression of Lnczc3h7a increased in response to RNA viruses, the lack of Lnczc3h7a abrogated type I IFN signaling and elevated the replication of RNA viruses both in vitro and in vivo. How does Lnczc3h7a promote type I-IFN-mediated antiviral innate immunity? The authors showed that Lnczc3h7a serves as a scaffold to stabilize the RIG-I–TRIM25 complex and facilitates the TRIM25-mediated K63-linked ubiquitination of RIG-I by microscopic colocalization and coimmunoprecipitation assays and an RNA pull-down assay. Furthermore, Lin et al. suggested the binding sites for TRIM25 and RIG-I in Lnczc3h7a.

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Acknowledgements

We thank Edanz (www.edanzediting.co.jp) for editing the English text of a draft of this paper.

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  1. Department of Respiratory Medicine, National Hospital Organization Osaka Toneyama Medical Center, Osaka, Japan

    Kiyoharu Fukushima & Hiroshi Kida

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  1. Kiyoharu Fukushima
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Correspondence to Hiroshi Kida.

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Fukushima, K., Kida, H. A host lncRNA regulates the innate immune response to an RNA virus. Cell Mol Immunol 16, 841–842 (2019). https://doi.org/10.1038/s41423-019-0280-7

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