Fu Yao, Zhao Xingli, Li Zhaohui, Wei Jun, Tian Yu
Department of Neurosurgery, China-Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China.
Oncol Lett. 2016 Aug;12(2):788-792. doi: 10.3892/ol.2016.4734. Epub 2016 Jun 15.
The roles of alternative splicing and RNA editing in gene regulation and transcriptome diversity are well documented. Adenosine deaminases acting on RNA (ADARs) are responsible for adenosine-to-inosine (A-to-I) editing and exemplify the complex association between RNA editing and alternative splicing. The self-editing activity of ADAR2, which acts on its own pre-mRNA, leads to its alternative splicing. Alternative splicing occurs independently at nine splicing sites on ADAR2 pre-mRNA, generating numerous alternative splicing variants with various catalytic activities. A-to-I RNA editing is important in a range of physiological processes in humans and is associated with several diseases, including amyotrophic lateral sclerosis, mood disorders, epilepsy and glioma. Reduced editing at the glutamine/arginine site of the AMPA receptor subunit GluA2 in glioma, without any alteration in ADAR2 expression, is a notable phenomenon. Several studies have tried to explain this alteration in the catalytic activity of ADAR2; however, the underlying mechanism remains unclear. The present review summarizes the relevant literature and shares experimental results concerning ADAR2 alternative splicing. In particular, the present review demonstrates that shifts in the relative abundance of the active and inactive splicing variants of ADAR2 may reduce the ADAR2 editing activity in glioma. Dominant expression of ADAR2 splicing variant with low enzyme activity causes reduced RNA editing of GluA2 subunit at the glutamine/arginine site in glioma.
可变剪接和RNA编辑在基因调控和转录组多样性中的作用已有充分记载。作用于RNA的腺苷脱氨酶（ADARs）负责腺苷到次黄苷（A到I）的编辑，体现了RNA编辑与可变剪接之间的复杂关联。ADAR2对自身前体mRNA进行自我编辑的活性，导致其发生可变剪接。可变剪接在ADAR2前体mRNA的九个剪接位点独立发生，产生具有各种催化活性的众多可变剪接变体。A到I RNA编辑在人类一系列生理过程中很重要，并与多种疾病相关，包括肌萎缩侧索硬化症、情绪障碍、癫痫和神经胶质瘤。神经胶质瘤中α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体亚基GluA2的谷氨酰胺/精氨酸位点编辑减少，而ADAR2表达没有任何改变，这是一个值得注意的现象。几项研究试图解释ADAR2催化活性的这种改变；然而其潜在机制仍不清楚。本综述总结了相关文献，并分享了关于ADAR2可变剪接的实验结果。特别是，本综述表明ADAR2活性和无活性剪接变体相对丰度的变化可能会降低神经胶质瘤中ADAR2的编辑活性。低酶活性的ADAR2剪接变体的显性表达导致神经胶质瘤中GluA2亚基在谷氨酰胺/精氨酸位点的RNA编辑减少。
