Transcriptional activation of the MICA gene with an engineered CRISPR-Cas9 system
Transcriptional activation of the MICA gene with an engineered CRISPR-Cas9 system
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DOI：
10.1016/j.bbrc.2017.03.076
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发表时间：
2017-04-29
影响因子：
3.1
通讯作者：
Koike, Kazuhiko
中科院分区：
文献类型：
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作者：
Sekiba, Kazuma;Yamagami, Mari;Koike, Kazuhiko
主要组织相容性复合体I类多肽相关序列A （MICA）是一种典型的NKG2D配体。由于免疫细胞，如自然杀伤（NK）细胞，通过NK细胞上的NKG2D受体和致病细胞上的NKG2D配体之间的相互作用识别病毒感染或转化的细胞并消除它们，MICA的表达水平与NK细胞介导的免疫有关。在这里，我们报道了一个工程集群规则间隔短回文重复cas9相关复合体靶向MICA基因启动子序列激活MICA基因的内源性位点的转录。抑制microRNA功能，其目标是MICA基因的3'非翻译区，增强了这种激活。这些结果表明，结合基于cas9的转录激活因子和同时调节microRNA功能可能是增强MICA蛋白表达和有效抗致病性细胞免疫的有力工具。(C) 2017爱思唯尔公司版权所有。
Major histocompatibility complex class I polypeptide-related sequence A (MICA) is a prototypical NKG2D ligand. Because immune cells, such as natural killer (NK) cells, recognize virally infected or transformed cells and eliminate them through the interaction between NKG2D receptors on NK cells and NKG2D ligands on pathogenic cells, MICA expression levels are associated with NK cell-mediated immunity. Here, we report that an engineered clustered regularly interspaced short palindromic repeats-Cas9-related complex targeting MICA gene promoter sequences activates transcription of the MICA gene from its endogenous locus. Inhibiting microRNA function, which targets the 3' untranslated region of the MICA gene, enhances this activation. These results demonstrate that the combination of Cas9-based transcriptional activators and simultaneous modulation of microRNA function may be a powerful tool for enhancing MICA protein expression and efficient anti-pathogenic cell immunity. (C) 2017 Elsevier Inc. All rights reserved.