2023年11月2日 · We demonstrate that discrete functions of ADAR1p150 determine MDA5 or PKR engagement: A-to-I editing of endogenous dsRNA specifically prevents MDA5 activation, whereas PKR activation is prevented by editing-independent, competitive dsRNA binding in the cytoplasm.

2018年2月8日 · ADAR1 dsRNA binding and catalytic activities were required to fully prevent endogenous RNA from activating PKR. Remarkably, ADAR1 knockout neuronal progenitor cells exhibited MDA5 (dsRNA sensor)-dependent spontaneous interferon production, PKR …

2016年3月3日 · Here, we provide evidence that PKR is involved in MDA5-mediated responses to virus infection and is necessary for IFN induction. Mechanistically, we found that MDA5 and PKR proteins associate in a complex, and that MDA5 augments virus-induced activation of PKR.

2016年3月3日 · Two cytosolic RIG-like RNA helicases, RIG-I and MDA5, are key to type I interferon (IFN) induction in response to viral infection. Mounting evidence suggests that another viral RNA sensor, protein kinase R (PKR) …

2 天之前 · The functions of MDA5, RIG-I and PKR are not redundant, and these proteins bind different RNA structures and motifs in a largely sequence-independent manner (Rehwinkel and Gack, 2020), but little is known about the exact endogenous dsRNAs that activates these proteins, and it is possible that they represent different RNA populations.

2 天之前 · Hu, S. B. et al. ADAR1p150 prevents MDA5 and PKR activation via distinct mechanisms to avert fatal autoinflammation. Mol. Cell 83, 3869–3884.e3867 (2023).

2024年8月27日 · Immunoblot analyses of total protein extracts from proximal intestines of P14 pups show that Adar Mavs intestines have increased expression of Pkr, Mda5, and Rig-I proteins compared to wild-type or Mavs intestines (Figures 4A and 4B). We cannot assess the activation state of Pkr protein in mice because antibodies against active ...

2019年1月7日 · 研究者采用 CRISPR 技术进行的全基因组编辑，发现，蛋白激酶 R （PKR）或黑色素瘤分化相关基因 5（MDA5）介导的 dsRNA 应激可以增强 Adar1-null 肿瘤对免疫检查点阻断的响应。

2023年11月2日 · We now demonstrate that the loss of ADAR1-mediated RNA editing specifically activates MDA5, whereas loss of the cytoplasmic ADAR1p150 isoform or its dsRNA-binding activity enabled PKR activation. Deleting both MDA5 and PKR resulted in complete rescue of the embryonic lethality of Adar1p150-/-mice to adulthood, contrasting with the limited or no ...

我们现在证明，adar1 介导的 rna 编辑的缺失会特异性激活 mda5，而细胞质 adar1p150 亚型或其 dsrna 结合活性的缺失则会激活 pkr。 删除 MDA5 和 PKR 可以完全挽救Adar1p150 -/−小鼠的胚胎致死性直至成年，而单独删除 MDA5 或 PKR 则只能有限或无法挽救。