Department of Pharmaceutical Sciences, College of Pharmacy, Glendale, AZ, USA.
Epigenetics. 2012 Oct;7(10):1094-7. doi: 10.4161/epi.21977. Epub 2012 Sep 4.
Several recent landmark papers describing N(6) -methyladenosine (m(6) A) RNA modifications have provided valuable new insights as to the importance of m(6) A in the RNA transcriptome and in furthering the understanding of RNA epigenetics. One endogenous enzyme responsible for demethylating RNA m(6) A, FTO, is highly expressed in the CNS and is likely involved in mRNA metabolism, splicing or other nuclear RNA processing events. microRNAs (miRNAs), a family of small, non-coding transcripts that bind to target mRNAs and inhibit subsequent translation, are highly expressed in the CNS and are associated with several neurological disorders, including epilepsy. miRNAs frequently bind to recognition sequences in the 3'UTR, a region that is also enriched for m(6) A. Certain specific miRNAs are upregulated by neuronal activity and are coupled to epileptogenesis; these miRNAs contain a consensus m(6) A site that if methylated could possibly regulate miRNA processing or function. This commentary highlights aspects from recent papers to propose a functional association between FTO, RNA epigenetics and epilepsy.
最近有几篇描述 N(6)-甲基腺苷(m(6)A)RNA 修饰的里程碑式论文，为 m(6)A 在 RNA 转录组中的重要性以及进一步理解 RNA 表观遗传学提供了有价值的新见解。一种负责去甲基化 RNA m(6)A 的内源性酶 FTO 在中枢神经系统中高度表达，可能参与 mRNA 代谢、剪接或其他核 RNA 加工事件。microRNAs (miRNAs)是一类小的非编码转录物，可与靶 mRNA 结合并抑制后续翻译，在中枢神经系统中高度表达，并与包括癫痫在内的几种神经疾病有关。miRNAs 经常与 3'UTR 中的识别序列结合，而该区域也富含 m(6)A。某些特定的 miRNAs 受神经元活动的上调，并与癫痫发生有关；这些 miRNAs 包含一个共识的 m(6)A 位点，如果甲基化，可能会调节 miRNA 的加工或功能。本评论从最近的论文中强调了 FTO、RNA 表观遗传学和癫痫之间的功能关联。
