Long noncoding RNA CHROMR regulates antiviral immunity in humans

被引：28

作者：

van Solingen, Coen ^{[1
]}

Cyr, Yannick ^{[1
]}

Scacalossi, Kaitlyn R. ^{[1
]}

de Vries, Maren ^{[2
]}

Barrett, Tessa J. ^{[1
]}

de Jong, Annika ^{[1
]}

Gourvest, Morgane ^{[1
]}

Zhang, Tracy

Peled, Daniel ^{[1
]}

Kher, Raadhika ^{[1
]}

Cornwell, MacIntosh ^{[3
]}

Gildea, Michael A. ^{[1
]}

Brown, Emily J. ^{[1
]}

Fanucchi, Stephanie ^{[4
]}

Mhlanga, Musa M. ^{[5
,6
,7
]}

Berger, Jeffrey S. ^{[1
]}

Dittmann, Meike ^{[2
]}

Moore, Kathryn J. ^{[1
,8
]}

机构：

[1] New York Univ Langone Hlth, Leon H Charney Div Cardiol, Dept Med, NYU Cardiovasc Res Ctr, New York, NY 10016 USA

[2] New York Univ Langone Hlth, Dept Microbiol, New York, NY 10016 USA

[3] New York Univ Langone Hlth, Inst Syst Genet, Dept Med, New York, NY 10016 USA

[4] Lemba Therapeut BV, NL-6525 GA Nijmegen, Netherlands

[5] Radboud Univ Nijmegen, Dept Cell Biol FNWI, Epigen & Single Cell Biophys Grp, NL-6500 HB Nijmegen, Netherlands

[6] Radboud Univ Nijmegen Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands

[7] Radboud Inst Mol Life Sci, NL-6500 HB Nijmegen, Netherlands

[8] New York Univ Sch Med, Dept Cell Biol, New York, NY 10016 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2022年 / 119卷 / 37期

基金：

比尔及梅琳达.盖茨基金会; 加拿大健康研究院;

关键词：

lncRNA; innate immune signaling; interferon-stimulated genes; antiviral response; WEB; CHOLESTEROL; ANNOTATION; GENCODE; SERVER;

D O I：

10.1073/pnas.2210321119

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Long noncoding RNAs (lncRNAs) have emerged as critical regulators of gene expres-sion, yet their contribution to immune regulation in humans remains poorly under-stood. Here, we report that the primate-specific lncRNA CHROMR is induced by influenza A virus and SARS-CoV-2 infection and coordinates the expression of interferon-stimulated genes (ISGs) that execute antiviral responses. CHROMR deple-tion in human macrophages reduces histone acetylation at regulatory regions of ISG loci and attenuates ISG expression in response to microbial stimuli. Mechanistically, we show that CHROMR sequesters the interferon regulatory factor (IRF)-2-dependent transcriptional corepressor IRF2BP2, thereby licensing IRF-dependent signaling and transcription of the ISG network. Consequently, CHROMR expression is essential to restrict viral infection of macrophages. Our findings identify CHROMR as a key arbitra-tor of antiviral innate immune signaling in humans.

引用

页数：9

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