细胞质中的双链RNA(dsRNA)可通过被细胞质内的dsRNA感知器,如MDA5、RIG-I和PKR等,识别并触发固有免疫应答。一旦dsRNA被识别,MDA5或RIG-I会激活干扰素信号通路,而PKR则会抑制蛋白翻译。这些反应有助于保护细胞免受病原性dsRNA(例如病...
ADAR1是RNA表观修饰的重要蛋白,可以通过修饰dsRNA,阻断MDA5-MAVS下游通路,抑制干扰素(IFN)的释放,从而抑制炎症反应。因此,近年来关于ADAR1在肿瘤免疫治疗中的应用也有较多报道。我们团队将研究重点放在结直肠癌领域,以补充现有的相关结论...
其中，脱氨酶结构域能够催化dsRNA的A-to-I编辑，Zα结构域能够特异性识别和结合左旋核酸（Z-nucleic acids，Z-NAs）。大部分ADAR1 突变诱发的 AGS 患者携带ADAR1基因复合杂合突变：Zα结构域突变（P193A）和功能丧失性突变（移码突变或脱氨酶结构域突变）【1】，模拟该类AGS患者的小鼠模型表现出MDA5-MAVS依赖的...
在病毒感染期间,长链外源dsRNA被MDA5、PKR和OAS识别,启动三个途径导致细胞凋亡以防止病毒的复制。MDA5途径导致干扰素(IFN)基因的诱导表达,这对于对抗病毒感染至关重要。然而,在没有病毒感染的情况下,内源dsRNA会被ADAR1修饰,从而阻止它们被这些先天免疫传感器识别。 3.ADAR1 参与 microRNA(miRNA)加工和功能调节。pri...
ADAR1p150调控线粒体抗病毒信号蛋白(MAVS)、黑素瘤分化相关蛋白5 (MDA5)和干扰素信号(MDA5-MAVS- ifn信号)介导的dsrna传感机制。对癌症基因组图谱数据库的分析显示,几乎在所有类型的癌症中,ADAR1的表达和A-to-I编辑水平升高,这表明这种促癌基因ADAR1p150的功能有助于癌细胞抑制炎症反应,从而避免宿主的免疫监视...
Adenosine deaminase acting on RNA 1 (ADAR1) is the enzyme responsible for adenosine-to-inosine RNA editing in dsRNAs, and loss of ADAR1 activates the innate immune sensing response via melanoma differentiation-associated protein 5 (MDA5), which interprets unedited dsRNA as non-self. Although ...
RNA EDITING RNA editing by ADAR1 prevents MDA5 sensing of endogenous dsRNA as nonselfAdenosine-to-inosine (A-to-I) editing is a highlyWalkley... Walkley,Carl,R.,... - 《Science》 被引量: 0发表: 2015年 Functions of the RNA Editing Enzyme ADAR1 and Their Relevance to Human Diseases Ad...
2 Even partial loss of RNA-editing activity in mice carrying the catalytic domain K999N and D1113H mutations leads to MDA5-dependent dsRNA-sensing signaling pathway activation.25,26,27 These results support the hypothesis that unedited endogenous RNAs trigger the MDA5 RNA sensor, leading to the...
ADAR1是一种双链RNA(dsRNA)上的腺苷脱氨酶,可以将腺苷(A)转化为肌苷(I),这一过程被称为A-to-I编辑。ADAR1的缺失或功能障碍会导致严重的炎症反应,而其在肿瘤细胞中则起到促进肿瘤进展和免疫逃逸的作用。因此,ADAR1成为了药物开发的一个新兴靶点。文章重点讨论了ADAR1的结构、功能、以及在免疫应答和疾病进展中...
Although ADAR1-mediated adenosine to inosine (A-to-I) editing is known to limit the accumulation of immunostimulatory endogenous double-stranded RNA (dsRNA) that signals through MDA5–MAVS, the downstream pathways responsible for autoinflammation in the context of ADAR mutation have not been fully ...