Wang Qingde, Li Xiaoni, Qi Ruofan, Billiar Timothy
Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Genes (Basel). 2017 Jan 18;8(1):41. doi: 10.3390/genes8010041.
RNA editing, particularly A-to-I RNA editing, has been shown to play an essential role in mammalian embryonic development and tissue homeostasis, and is implicated in the pathogenesis of many diseases including skin pigmentation disorder, autoimmune and inflammatory tissue injury, neuron degeneration, and various malignancies. A-to-I RNA editing is carried out by a small group of enzymes, the adenosine deaminase acting on RNAs (ADARs). Only three members of this protein family, ADAR1-3, exist in mammalian cells. ADAR3 is a catalytically null enzyme and the most significant function of ADAR2 was found to be in editing on the neuron receptor GluR-B mRNA. ADAR1, however, has been shown to play more significant roles in biological and pathological conditions. Although there remains much that is not known about how ADAR1 regulates cellular function, recent findings point to regulation of the innate immune response as an important function of ADAR1. Without appropriate RNA editing by ADAR1, endogenous RNA transcripts stimulate cytosolic RNA sensing receptors and therefore activate the IFN-inducing signaling pathways. Overactivation of innate immune pathways can lead to tissue injury and dysfunction. However, obvious gaps in our knowledge persist as to how ADAR1 regulates innate immune responses through RNA editing. Here, we review critical findings from ADAR1 mechanistic studies focusing on its regulatory function in innate immune responses and identify some of the important unanswered questions in the field.
RNA编辑，尤其是A-to-I RNA编辑，已被证明在哺乳动物胚胎发育和组织稳态中发挥着至关重要的作用，并且与许多疾病的发病机制有关，包括皮肤色素沉着紊乱、自身免疫和炎症性组织损伤、神经元变性以及各种恶性肿瘤。A-to-I RNA编辑由一小类酶——作用于RNA的腺苷脱氨酶（ADARs）进行。在哺乳动物细胞中，这个蛋白质家族只有三个成员，即ADAR1 - 3。ADAR3是一种无催化活性的酶，并且发现ADAR2的最重要功能是对神经元受体GluR - B mRNA进行编辑。然而，ADAR1已被证明在生物学和病理学条件下发挥更重要的作用。尽管关于ADAR1如何调节细胞功能仍有许多未知之处，但最近的研究结果表明，调节先天免疫反应是ADAR1的一项重要功能。如果没有ADAR1进行适当的RNA编辑，内源性RNA转录本会刺激胞质RNA传感受体，从而激活诱导IFN的信号通路。先天免疫途径的过度激活会导致组织损伤和功能障碍。然而，关于ADAR1如何通过RNA编辑调节先天免疫反应，我们的知识仍存在明显空白。在这里，我们回顾了ADAR1机制研究的关键发现，重点关注其在先天免疫反应中的调节功能，并确定了该领域一些重要的未解决问题。
