RNA helicase SKIV2L limits antiviral defense and autoinflammation elicited by the OAS-RNase L pathway.

IF 9.4 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY EMBO Journal Pub Date : 2024-08-07 DOI:10.1038/s44318-024-00187-1
Kun Yang, Beihua Dong, Abhishek Asthana, Robert H Silverman, Nan Yan
{"title":"RNA helicase SKIV2L limits antiviral defense and autoinflammation elicited by the OAS-RNase L pathway.","authors":"Kun Yang, Beihua Dong, Abhishek Asthana, Robert H Silverman, Nan Yan","doi":"10.1038/s44318-024-00187-1","DOIUrl":null,"url":null,"abstract":"<p><p>The OAS-RNase L pathway is one of the oldest innate RNA sensing pathways that leads to interferon (IFN) signaling and cell death. OAS recognizes viral RNA and then activates RNase L, which subsequently cleaves both cellular and viral RNA, creating \"processed RNA\" as an endogenous ligand that further triggers RIG-I-like receptor signaling. However, the IFN response and antiviral activity of the OAS-RNase L pathway are weak compared to other RNA-sensing pathways. Here, we discover that the SKIV2L RNA exosome limits the antiviral capacity of the OAS-RNase L pathway. SKIV2L-deficient cells exhibit remarkably increased interferon responses to RNase L-processed RNA, resulting in heightened antiviral activity. The helicase activity of SKIV2L is indispensable for this function, acting downstream of RNase L. SKIV2L depletion increases the antiviral capacity of OAS-RNase L against RNA virus infection. Furthermore, SKIV2L loss exacerbates autoinflammation caused by human OAS1 gain-of-function mutations. Taken together, our results identify SKIV2L as a critical barrier to OAS-RNase L-mediated antiviral immunity that could be therapeutically targeted to enhance the activity of a basic antiviral pathway.</p>","PeriodicalId":50533,"journal":{"name":"EMBO Journal","volume":null,"pages":null},"PeriodicalIF":9.4000,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"EMBO Journal","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1038/s44318-024-00187-1","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

The OAS-RNase L pathway is one of the oldest innate RNA sensing pathways that leads to interferon (IFN) signaling and cell death. OAS recognizes viral RNA and then activates RNase L, which subsequently cleaves both cellular and viral RNA, creating "processed RNA" as an endogenous ligand that further triggers RIG-I-like receptor signaling. However, the IFN response and antiviral activity of the OAS-RNase L pathway are weak compared to other RNA-sensing pathways. Here, we discover that the SKIV2L RNA exosome limits the antiviral capacity of the OAS-RNase L pathway. SKIV2L-deficient cells exhibit remarkably increased interferon responses to RNase L-processed RNA, resulting in heightened antiviral activity. The helicase activity of SKIV2L is indispensable for this function, acting downstream of RNase L. SKIV2L depletion increases the antiviral capacity of OAS-RNase L against RNA virus infection. Furthermore, SKIV2L loss exacerbates autoinflammation caused by human OAS1 gain-of-function mutations. Taken together, our results identify SKIV2L as a critical barrier to OAS-RNase L-mediated antiviral immunity that could be therapeutically targeted to enhance the activity of a basic antiviral pathway.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
RNA 螺旋酶 SKIV2L 限制了 OAS-RNase L 途径引起的抗病毒防御和自身炎症。
OAS-RNase L通路是最古老的先天RNA感应通路之一,可导致干扰素(IFN)信号传导和细胞死亡。OAS 能识别病毒 RNA,然后激活 RNase L,RNase L 随后会裂解细胞和病毒 RNA,产生 "加工过的 RNA "作为内源性配体,进一步触发 RIG-I 样受体信号。然而,与其他 RNA 传感途径相比,OAS-RNase L 途径的 IFN 反应和抗病毒活性较弱。在这里,我们发现 SKIV2L RNA 外泌体限制了 OAS-RNase L 途径的抗病毒能力。SKIV2L 缺陷细胞对 RNase L 处理过的 RNA 的干扰素反应明显增加,导致抗病毒活性增强。SKIV2L 的螺旋酶活性对这一功能不可或缺,它在 RNase L 的下游发挥作用。此外,SKIV2L 的缺失会加剧人类 OAS1 功能增益突变引起的自身炎症。综上所述,我们的研究结果表明,SKIV2L 是 OAS-RNase L 介导的抗病毒免疫的一个关键障碍,可以通过治疗来增强基本抗病毒途径的活性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
EMBO Journal
EMBO Journal 生物-生化与分子生物学
CiteScore
18.90
自引率
0.90%
发文量
246
审稿时长
1.5 months
期刊介绍: The EMBO Journal has stood as EMBO's flagship publication since its inception in 1982. Renowned for its international reputation in quality and originality, the journal spans all facets of molecular biology. It serves as a platform for papers elucidating original research of broad general interest in molecular and cell biology, with a distinct focus on molecular mechanisms and physiological relevance. With a commitment to promoting articles reporting novel findings of broad biological significance, The EMBO Journal stands as a key contributor to advancing the field of molecular biology.
期刊最新文献
Author Correction: Limited oxygen in standard cell culture alters metabolism and function of differentiated cells. Histamine synthesis and transport are coupled in axon terminals via a dual quality control system. Disordered regions in the IRE1α ER lumenal domain mediate its stress-induced clustering. Structure of tetrameric forms of the serotonin-gated 5-HT3A receptor ion channel. Elucidating the assembly of gas vesicles by systematic protein-protein interaction analysis.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1