Laxminarayana Dama, Khan Islam U, O'Rourke Kenneth S, Giri Banabihari
Section on Rheumatology and Immunology, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Immunology. 2007 Dec;122(4):623-33. doi: 10.1111/j.1365-2567.2007.02709.x. Epub 2007 Sep 25.
We and other investigators have demonstrated up-regulation of the expression of the RNA-editing gene 150-kDa adenosine deaminase that acts on RNA (ADAR1) in systemic lupus erythematosus (SLE) T cells and B cells, peripheral blood mononuclear cells (PBMC), natural killer (NK) cells. The presence of a small proportion of activated T cells is the hallmark of SLE. Therefore, it was hypothesized that 150-kDa ADAR1 gene expression is induced by the physiological activation of T cells. To examine this hypothesis, normal T cells were activated by anti-CD3-epsilon plus anti-CD28 for various time periods from 0 to 48 hr. The expression of 110-kDa and 150-kDa ADAR1, and interleukin (IL)-2 and beta-actin gene transcripts was analysed. An approximately fourfold increase in 150-kDa ADAR1 gene expression was observed in activated T cells. ADAR2 gene transcripts are substrates for ADAR1 and ADAR2 enzymes. Therefore, we assessed the role of the 150-kDa ADAR enzyme in editing of ADAR2 gene transcripts. In activated T cells, site-selective editing of the -2 site was observed. Previous studies indicate that this site is predominantly edited by ADAR1. In addition to this, novel editing sites at base positions -56, -48, -45, -28, -19, -15, +46 and +69 were identified in activated T cells. On the basis of these results, it is proposed that 150-kDa ADAR1 gene expression is selectively induced in T cells by anti-CD3-epsilon and anti-CD28 stimulation and that it may play a role in site-selective editing of gene transcripts and in altering the functions of several gene products of T cells during activation and proliferation.
我们和其他研究人员已证明，在系统性红斑狼疮（SLE）的T细胞、B细胞、外周血单核细胞（PBMC）及自然杀伤（NK）细胞中，作用于RNA的RNA编辑基因150 kDa腺苷脱氨酶（ADAR1）的表达上调。一小部分活化T细胞的存在是SLE的标志。因此，有人提出假设，150 kDa ADAR1基因表达是由T细胞的生理活化诱导的。为检验这一假设，用抗CD3-ε加抗CD28在0至48小时的不同时间段激活正常T细胞。分析了110 kDa和150 kDa ADAR1以及白细胞介素（IL）-2和β-肌动蛋白基因转录本的表达。在活化的T细胞中观察到150 kDa ADAR1基因表达增加了约四倍。ADAR2基因转录本是ADAR1和ADAR2酶的底物。因此，我们评估了150 kDa ADAR酶在ADAR2基因转录本编辑中的作用。在活化的T细胞中，观察到-2位点的位点选择性编辑。先前的研究表明，该位点主要由ADAR1编辑。除此之外，在活化的T细胞中还鉴定出了位于碱基位置-56、-48、-45、-28、-19、-15、+46和+69的新编辑位点。基于这些结果，有人提出，抗CD3-ε和抗CD28刺激可在T细胞中选择性诱导150 kDa ADAR1基因表达，并且它可能在基因转录本的位点选择性编辑以及在T细胞活化和增殖过程中改变几种基因产物的功能方面发挥作用。
