Dysregulated A to I RNA editing and non-coding RNAs in neurodegeneration.
Dysregulated A to I RNA editing and non-coding RNAs in neurodegeneration.
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DOI：
10.3389/fgene.2012.00326
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发表时间：
2012
影响因子：
3.7
通讯作者：
Singh M
中科院分区：
文献类型：
--
作者：
Singh M
RNA编辑是由于碱基的化学变化而导致的初级核苷酸序列的改变。RNA编辑存在于真核细胞的RNA、转移RNA、核糖体RNA和非编码RNA(NcRNA)中。哺乳动物中枢神经系统中最常见的RNA编辑是碱基修饰，其中腺苷残基被碱基修饰为肌苷(A到I)。对秀丽线虫、果蝇和小鼠的ADAR(作用于RNA的腺苷脱氨酶)突变体的研究清楚地表明，RNA编辑过程是动物神经系统动态平衡和正常生理的绝对要求。了解编辑机制和编辑底物的发现提供了更好的知识，由于缺陷和过度活跃的RNA编辑的表型。A to i RNA编辑是由一系列被称为ADAR的酶催化的。ADARS修饰双链RNA，编辑由ncRNAs形成的双链RNA，可以影响RNA的功能，导致调控基因网络的改变。这种通过A to I编辑而改变的功能在mRNAs、microRNAs(MiRNA)中观察到，但其他对小和长ncRNAs(LncRNAs)的编辑尚未确定。因此，ncRNA和RNA编辑可能在神经发育、神经系统功能和神经系统疾病之间提供关键联系。这篇综述包括关于ncRNAs对生物学和病理过程的影响的开创性发现的总结，这可能会通过RNA编辑来进一步修改。NcRNAs是根据大小和功能分类的非翻译RNA。已知的ncRNAs如miRNAs、SmRNAs(SmRNAs)、PIWI相互作用RNAs(PiRNAs)和lncRNAs在剪接、DNA甲基化、印迹和RNA干扰中发挥重要作用。值得注意的是，miRNAs参与神经系统的发育和功能，这在很大程度上依赖于RNA编辑和ncRNAs复杂的时空表达。这篇综述主要集中在失调的A到I编辑和ncRNAs在神经退行性变中的影响。
RNA editing is an alteration in the primary nucleotide sequences resulting from a chemical change in the base. RNA editing is observed in eukaryotic mRNA, transfer RNA, ribosomal RNA, and non-coding RNAs (ncRNA). The most common RNA editing in the mammalian central nervous system is a base modification, where the adenosine residue is base-modified to inosine (A to I). Studies from ADAR (adenosine deaminase that act on RNA) mutants in Caenorhabditis elegans, Drosophila, and mice clearly show that the RNA editing process is an absolute requirement for nervous system homeostasis and normal physiology of the animal. Understanding the mechanisms of editing and findings of edited substrates has provided a better knowledge of the phenotype due to defective and hyperactive RNA editing. A to I RNA editing is catalyzed by a family of enzymes knows as ADARs. ADARs modify duplex RNAs and editing of duplex RNAs formed by ncRNAs can impact RNA functions, leading to an altered regulatory gene network. Such altered functions by A to I editing is observed in mRNAs, microRNAs (miRNA) but other editing of small and long ncRNAs (lncRNAs) has yet to be identified. Thus, ncRNA and RNA editing may provide key links between neural development, nervous system function, and neurological diseases. This review includes a summary of seminal findings regarding the impact of ncRNAs on biological and pathological processes, which may be further modified by RNA editing. NcRNAs are non-translated RNAs classified by size and function. Known ncRNAs like miRNAs, smallRNAs (smRNAs), PIWI-interacting RNAs (piRNAs), and lncRNAs play important roles in splicing, DNA methylation, imprinting, and RNA interference. Of note, miRNAs are involved in development and function of the nervous system that is heavily dependent on both RNA editing and the intricate spatiotemporal expression of ncRNAs. This review focuses on the impact of dysregulated A to I editing and ncRNAs in neurodegeneration.