The 2'-O-methylation status of a single guanosine controls transfer RNA-mediated Toll-like receptor 7 activation or inhibition.
The 2'-O-methylation status of a single guanosine controls transfer RNA-mediated Toll-like receptor 7 activation or inhibition.
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DOI：
10.1084/jem.20111075
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发表时间：
2012-02-13
期刊：
影响因子：
--
通讯作者：
Bauer S
中科院分区：
文献类型：
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作者：
Jöckel S;Nees G;Sommer R;Zhao Y;Cherkasov D;Hori H;Ehm G;Schnare M;Nain M;Kaufmann A;Bauer S
由于鸟苷修饰的存在，细菌转移RNA可以抑制其他细菌trna的免疫刺激活性。外源RNA作为病原体相关分子模式（PAMP），是先天免疫受体的有效免疫刺激物。然而，单一细菌RNA物种在免疫激活中的作用尚未被详细表征。我们分析了来自不同细菌的转移RNA （tRNA）的免疫刺激潜能。有趣的是，细菌tRNA在小鼠树突状细胞（dc）和人外周血单核细胞（PBMCs）中诱导I型干扰素（IFN）和炎症细胞因子。细胞因子的产生依赖于TLR7，因为TLR7缺陷小鼠dc没有反应，TLR7抑制寡核苷酸抑制trna介导的激活。然而，并不是所有的细菌tRNA都能诱导IFN-α，因为来自大肠杆菌Nissle 1917和嗜热热菌的tRNA是非免疫刺激的。值得注意的是，tRNA (Gm18)-2 ' - o -甲基转移酶（trmH）的大肠杆菌敲除菌株的tRNA恢复了免疫刺激潜能。此外，用来自嗜热t菌的重组trmH体外甲基化这种免疫刺激性gm18阴性tRNA，可消除其诱导IFN-α的潜力。更重要的是，gm18修饰的tRNA可作为TLR7拮抗剂，阻断IFN-α诱导甲型流感病毒感染的pbmc。
Bacterial transfer RNA can suppress the immunostimulatory activity of other bacterial tRNAs as a result of the presence of a guanosine modification. Foreign RNA serves as pathogen-associated molecular pattern (PAMP) and is a potent immune stimulator for innate immune receptors. However, the role of single bacterial RNA species in immune activation has not been characterized in detail. We analyzed the immunostimulatory potential of transfer RNA (tRNA) from different bacteria. Interestingly, bacterial tRNA induced type I interferon (IFN) and inflammatory cytokines in mouse dendritic cells (DCs) and human peripheral blood mononuclear cells (PBMCs). Cytokine production was TLR7 dependent because TLR7-deficient mouse DCs did not respond and TLR7 inhibitory oligonucleotides inhibited tRNA-mediated activation. However, not all bacterial tRNA induced IFN-α because tRNA from Escherichia coli Nissle 1917 and Thermus thermophilus were non-immunostimulatory. Of note, tRNA from an E. coli knockout strain for tRNA (Gm18)-2′-O-methyltransferase (trmH) regained immunostimulatory potential. Additionally, in vitro methylation of this immunostimulatory Gm18-negative tRNA with recombinant trmH from T. thermophilus abolished its IFN-α inducing potential. More importantly, Gm18-modified tRNA acted as TLR7 antagonist and blocked IFN-α induction of influenza A virus–infected PBMCs.
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影响因子：
3.2
作者：
De Bie, LGS;Roovers, M;Bujnicki, JM
通讯作者：
Bujnicki, JM
影响因子：
2.8
作者：
Hamm, Svetlana;Latz, Eicke;Bauer, Stefan
通讯作者：
Bauer, Stefan
影响因子：
4.8
作者：
Ochi, Anna;Makabe, Koki;Hori, Hiroyuki
通讯作者：
Hori, Hiroyuki
影响因子：
14.9
作者：
Persson, BC;Jager, G;Gustafsson, C
通讯作者：
Gustafsson, C
病毒mRNA帽的2'-O甲基化通过IFIT家族成员逃避了宿主的限制。
影响因子：
64.8
作者：
通讯作者：
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