METTL3 regulates viral m6A RNA modification and host cell innate immune responses during SARS-CoV-2 infection.
METTL3 regulates viral m6A RNA modification and host cell innate immune responses during SARS-CoV-2 infection.
复制标题
METTL3调节SARS-COV-2感染期间的病毒M6A RNA修饰和宿主细胞先天免疫反应。
DOI：
10.1016/j.celrep.2021.109091
复制
发表时间：
2021-05-11
期刊：
影响因子：
8.8
通讯作者：
Rana TM
中科院分区：
文献类型：
--
作者：
Li N;Hui H;Bray B;Gonzalez GM;Zeller M;Anderson KG;Knight R;Smith D;Wang Y;Carlin AF;Rana TM
了解广泛传播的严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）与宿主免疫应答的关系，并研究其分子机制，具有重要的现实意义。RNA中腺苷（m6A）的N6-甲基化调节许多生理和疾病过程。在这里，我们调查m6A修饰的SARS-CoV-2基因在调节宿主细胞的先天免疫反应。我们的数据表明，SARS-CoV-2病毒具有富集在病毒基因组3 ′端的m6A修饰。我们发现宿主细胞m6A甲基转移酶L3的耗竭降低了SARS-CoV-2和宿主基因中m6A的水平，病毒RNA中m6A的减少增加了RIG-I的结合，随后增强了下游先天免疫信号通路和炎症基因的表达。2019冠状病毒病（COVID-19）重症患者的胃L3表达减少，炎症基因被诱导。这些发现将有助于理解COVID-19的发病机制，并设计未来调节先天免疫以治疗COVID-19的研究。li等人表明SARS-CoV-2 RNA含有腺苷（m6A）修饰的N6-甲基化，其在3 ′端富集，在逃避宿主对病毒感染的免疫反应中发挥作用。宿主细胞m6A甲基转移酶L3在SARS-CoV-2 RNA中添加m6A修饰，导致RIG-I结合减少，随后抑制先天免疫应答的感知和激活。
It is urgent and important to understand the relationship of the widespread severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2) with host immune response and study the underlining molecular mechanism. N6-methylation of adenosine (m6A) in RNA regulates many physiological and disease processes. Here, we investigate m6A modification of the SARS-CoV-2 gene in regulating the host cell innate immune response. Our data show that the SARS-CoV-2 virus has m6A modifications that are enriched in the 3′ end of the viral genome. We find that depletion of the host cell m6A methyltransferase METTL3 decreases m6A levels in SARS-CoV-2 and host genes, and m6A reduction in viral RNA increases RIG-I binding and subsequently enhances the downstream innate immune signaling pathway and inflammatory gene expression. METTL3 expression is reduced and inflammatory genes are induced in patients with severe coronavirus disease 2019 (COVID-19). These findings will aid in the understanding of COVID-19 pathogenesis and the design of future studies regulating innate immunity for COVID-19 treatment. Li et al. show that SARS-CoV-2 RNA contains N6-methylation of adenosine (m6A) modifications enriched at the 3′ end that play roles in evading host immune responses to viral infection. Host cell m6A methyltransferase METTL3 adds m6A modifications in SARS-CoV-2 RNA, leading to decreased RIG-I binding and subsequently dampening the sensing and activation of innate immune responses.
登录
查看更多内容
影响因子：
6.4
作者：
Durbin AF;Wang C;Marcotrigiano J;Gehrke L
通讯作者：
Gehrke L
影响因子：
64.5
作者：
Daniloski Z;Jordan TX;Wessels HH;Hoagland DA;Kasela S;Legut M;Maniatis S;Mimitou EP;Lu L;Geller E;Danziger O;Rosenberg BR;Phatnani H;Smibert P;Lappalainen T;tenOever BR;Sanjana NE
通讯作者：
Sanjana NE
影响因子：
29.7
作者：
Brubaker SW;Bonham KS;Zanoni I;Kagan JC
通讯作者：
Kagan JC
影响因子：
4.8
作者：
Kim, Geon-Woo;Imam, Hasan;Siddiqui, Aleem
通讯作者：
Siddiqui, Aleem
影响因子：
168.9
作者：
Huang, Chaolin;Wang, Yeming;Cao, Bin
通讯作者：
Cao, Bin