George Cyril X, John Lijo, Samuel Charles E
Department of Molecular, Cellular and Developmental Biology, University of California , Santa Barbara, California.
J Interferon Cytokine Res. 2014 Jun;34(6):437-46. doi: 10.1089/jir.2014.0001.
Adenosine deaminase acting on RNA1 (ADAR1) catalyzes the C6 deamination of adenosine (A) to produce inosine (I) in regions of RNA with double-stranded (ds) character. This process is known as A-to-I RNA editing. Alternative promoters drive the expression of the Adar1 gene and alternative splicing gives rise to transcripts that encode 2 ADAR1 protein size isoforms. ADAR1 p150 is an interferon (IFN)-inducible dsRNA adenosine deaminase found in the cytoplasm and nucleus, whereas ADAR1 p110 is constitutively expressed and nuclear in localization. Dependent on the duplex structure of the dsRNA substrate, deamination of adenosine by ADAR can be either highly site-selective or nonspecific. A-to-I editing can alter the stability of RNA structures and the coding of RNA as I is read as G instead of A by ribosomes during mRNA translation and by polymerases during RNA replication. A-to-I editing is of broad physiologic significance. Both the production and the action of IFNs, and hence the subsequent interaction of viruses with their hosts, are among the processes affected by A-to-I editing.
作用于RNA1的腺苷脱氨酶(ADAR1)催化腺苷(A)的C6脱氨基反应,在具有双链(ds)特征的RNA区域产生肌苷(I)。这个过程被称为A到I的RNA编辑。可变启动子驱动Adar1基因的表达,可变剪接产生编码两种ADAR1蛋白大小异构体的转录本。ADAR1 p150是一种在细胞质和细胞核中发现的干扰素(IFN)诱导型双链RNA腺苷脱氨酶,而ADAR1 p110是组成型表达且定位于细胞核。根据双链RNA底物的双链结构,ADAR对腺苷的脱氨基作用可以是高度位点选择性的,也可以是非特异性的。A到I的编辑可以改变RNA结构的稳定性以及RNA的编码,因为在mRNA翻译过程中核糖体将I读为G而非A,在RNA复制过程中聚合酶也是如此。A到I的编辑具有广泛的生理意义。干扰素的产生和作用,以及随后病毒与其宿主的相互作用,都是受A到I编辑影响的过程。