Chi Jie-Shan, Li Jian-Zhou, Jia Jing-Jing, Zhang Ting, Liu Xiao-Ma, Yi Li
Department of Neurology, Peking University Shenzhen Hospital, Shenzhen, 518000, China.
Shantou University Medical College, Shantou, 515041, China.
J Huazhong Univ Sci Technolog Med Sci. 2017 Dec;37(6):816-822. doi: 10.1007/s11596-017-1812-y. Epub 2017 Dec 21.
The antisense transcript long non-coding RNA (lncRNA) (antisense non-coding RNA in the INK4 locus, ANRIL) is an antisense of the cyclin-dependent kinase inhibitor 2B (CDKN2B) gene on chromosome 9p21 that contains an overlapping 299-bp region and shares a bidirectional promoter with alternate open reading frame (ARF). In the context of gene regulation, ANRIL is responsible for directly recruiting polycomb group (PcG) proteins, including polycomb repressive complex-1 (PRC-1) and polycomb repressive complex-2 (PRC-2), to modify the epigenetic chromatin state and subsequently inhibit gene expression in cis-regulation. On the other hand, previous reports have indicated that ANRIL is capable of binding to a specific site or sequence, including the Alu element, E2F transcription factor 1 (E2F1), and CCCTC-binding factor (CTCF), to achieve trans-regulation functions. In addition to its function in cell proliferation, adhesion and apoptosis, ANRIL is very closely associated with atherosclerosis- related diseases. The different transcripts and the SNPs that are related to atherosclerotic vascular diseases (ASVD-SNPs) are inextricably linked to the development and progression of atherosclerosis. Linear transcripts have been shown to be a risk factor for atherosclerosis, whereas circular transcripts are protective against atherosclerosis. Furthermore, ANRIL also acts as a component of the inflammatory pathway involved in the regulation of inflammation, which is considered to be one of the causes of atherosclerosis. Collectively, ANRIL plays an important role in the formation of atherosclerosis, and the artificial modification of ANRIL transcripts should be considered following the development of this disease.
反义转录长链非编码RNA（lncRNA）（INK4基因座中的反义非编码RNA，ANRIL）是9号染色体p21上细胞周期蛋白依赖性激酶抑制剂2B（CDKN2B）基因的反义转录物，它包含一个299碱基对的重叠区域，并与交替开放阅读框（ARF）共享一个双向启动子。在基因调控方面，ANRIL负责直接招募多梳蛋白家族（PcG）蛋白，包括多梳抑制复合物1（PRC-1）和多梳抑制复合物2（PRC-2），以修饰表观遗传染色质状态，随后在顺式调控中抑制基因表达。另一方面，先前的报道表明，ANRIL能够与特定位点或序列结合，包括Alu元件、E2F转录因子1（E2F1）和CCCTC结合因子（CTCF），以实现反式调控功能。除了在细胞增殖、黏附和凋亡中的作用外，ANRIL与动脉粥样硬化相关疾病密切相关。与动脉粥样硬化性血管疾病相关的不同转录本和单核苷酸多态性（ASVD-SNPs）与动脉粥样硬化的发生和发展有着千丝万缕的联系。线性转录本已被证明是动脉粥样硬化的一个危险因素，而环状转录本则对动脉粥样硬化具有保护作用。此外，ANRIL还作为炎症途径的一个组成部分参与炎症调节过程，炎症被认为是动脉粥样硬化的病因之一。总的来说，ANRIL在动脉粥样硬化的形成中起着重要作用，随着这种疾病的发展，应考虑对ANRIL转录本进行人工修饰。
