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<p>Interferon (IFN) signalling is essential for antiviral defence yet pathogenic in autoimmunity, however, the mechanisms orchestrating this duality remain poorly defined. Here, we identify <i>USP30-AS1</i>, a cytoplasmic long non-coding RNA (lncRNA) induced by type I IFN, as a pivotal post-transcriptional amplifier of innate immunity. We demonstrate that <i>USP30-AS1</i> selectively enhances the mRNA stability of nucleic acid sensors. Moreover, <i>USP30-AS1</i> preferentially stabilizes the majority of AU-rich element (ARE)-containing interferon-stimulated gene (ISG) mRNAs. <i>USP30-AS1</i> executes this function independently of its antisense partner, <i>USP30</i>. The deletion of <i>USP30-AS1</i> impaired IFN-β-mediated antiviral defence and suppressed pro-inflammatory cytokine production. Consistent with its role in amplifying immune responses, <i>USP30-AS1</i> was markedly upregulated in human autoimmune diseases characterised by dysregulated IFN signalling, including systemic lupus erythematosus, rheumatoid arthritis, and dermatomyositis. Thus, our work unveils <i>USP30-AS1</i> as a key regulator that fine-tunes the stability of nucleic acid sensors and ARE-containing immune transcripts, providing a direct mechanistic link between IFN signalling and post-transcriptional gene regulation. These findings establish <i>USP30-AS1</i> as a critical rheostat for immune homeostasis and a promising therapeutic target for IFN-associated diseases.</p>

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USP30-AS1 functions as a post-transcriptional amplifier of interferon signalling to drive autoimmune pathogenesis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月26日

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  • Jie Pan,
  • Min-Yi Feng,
  • Tian Xia,
  • Shuai Jiang,
  • Peng-Peng Zhu,
  • Xi-Ping Yu,
  • Zhi-Hui Su,
  • Yu Liu,
  • Jia-Qi Wu,
  • Ming Zhao,
  • Tao Li,
  • Wen Xue,
  • Yu Yu,
  • Liang Chen,
  • Hong Cai

摘要

Interferon (IFN) signalling is essential for antiviral defence yet pathogenic in autoimmunity, however, the mechanisms orchestrating this duality remain poorly defined. Here, we identify USP30-AS1, a cytoplasmic long non-coding RNA (lncRNA) induced by type I IFN, as a pivotal post-transcriptional amplifier of innate immunity. We demonstrate that USP30-AS1 selectively enhances the mRNA stability of nucleic acid sensors. Moreover, USP30-AS1 preferentially stabilizes the majority of AU-rich element (ARE)-containing interferon-stimulated gene (ISG) mRNAs. USP30-AS1 executes this function independently of its antisense partner, USP30. The deletion of USP30-AS1 impaired IFN-β-mediated antiviral defence and suppressed pro-inflammatory cytokine production. Consistent with its role in amplifying immune responses, USP30-AS1 was markedly upregulated in human autoimmune diseases characterised by dysregulated IFN signalling, including systemic lupus erythematosus, rheumatoid arthritis, and dermatomyositis. Thus, our work unveils USP30-AS1 as a key regulator that fine-tunes the stability of nucleic acid sensors and ARE-containing immune transcripts, providing a direct mechanistic link between IFN signalling and post-transcriptional gene regulation. These findings establish USP30-AS1 as a critical rheostat for immune homeostasis and a promising therapeutic target for IFN-associated diseases.