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What do editors do? Understanding the physiological functions of A-to-I RNA editing by adenosine deaminase acting on RNAs.
Open Biology ( IF 5.8 ) Pub Date : 2020-07-01 , DOI: 10.1098/rsob.200085
Jacki E Heraud-Farlow 1, 2 , Carl R Walkley 1, 2, 3
Affiliation  

Adenosine-to-inosine (A-to-I) editing is a post-transcriptional modification of RNA which changes its sequence, coding potential and secondary structure. Catalysed by the adenosine deaminase acting on RNA (ADAR) proteins, ADAR1 and ADAR2, A-to-I editing occurs at approximately 50 000–150 000 sites in mice and into the millions of sites in humans. The vast majority of A-to-I editing occurs in repetitive elements, accounting for the discrepancy in total numbers of sites between species. The species-conserved primary role of editing by ADAR1 in mammals is to suppress innate immune activation by unedited cell-derived endogenous RNA. In the absence of editing, inverted paired sequences, such as Alu elements, are thought to form stable double-stranded RNA (dsRNA) structures which trigger activation of dsRNA sensors, such as MDA5. A small subset of editing sites are within coding sequences and are evolutionarily conserved across metazoans. Editing by ADAR2 has been demonstrated to be physiologically important for recoding of neurotransmitter receptors in the brain. Furthermore, changes in RNA editing are associated with various pathological states, from the severe autoimmune disease Aicardi-Goutières syndrome, to various neurodevelopmental and psychiatric conditions and cancer. However, does detection of an editing site imply functional importance? Genetic studies in humans and genetically modified mouse models together with evolutionary genomics have begun to clarify the roles of A-to-I editing in vivo. Furthermore, recent developments suggest there may be the potential for distinct functions of editing during pathological conditions such as cancer.



中文翻译:

编辑是做什么的?了解腺苷脱氨酶作用于 RNA 的 A-to-I RNA 编辑的生理功能。

腺苷转肌苷 (A-to-I) 编辑是 RNA 的转录后修饰,可改变其序列、编码潜力和二级结构。在腺苷脱氨酶作用于 RNA (ADAR) 蛋白 ADAR1 和 ADAR2 的催化下,A-to-I 编辑发生在小鼠的大约 50 000-150 000 个位点和人类的数百万个位点。绝大多数 A-to-I 编辑发生在重复元素中,这说明了物种之间站点总数的差异。ADAR1 在哺乳动物中进行编辑的物种保守性主要作用是抑制未经编辑的细胞衍生内源性 RNA 的先天免疫激活。在没有编辑的情况下,反向配对序列,如Alu元素,被认为形成稳定的双链 RNA (dsRNA) 结构,触发 dsRNA 传感器的激活,如 MDA5。一小部分编辑位点位于编码序列内,并且在后生动物中进化保守。ADAR2 的编辑已被证明对大脑中神经递质受体的重新编码具有重要的生理意义。此外,RNA 编辑的变化与各种病理状态有关,从严重的自身免疫性疾病 Aicardi-Goutières 综合征到各种神经发育和精神疾病以及癌症。但是,检测到编辑站点是否意味着功能重要性?人类和转基因小鼠模型的遗传研究以及进化基因组学已经开始阐明体内A-to-I 编辑的作用. 此外,最近的发展表明,在癌症等病理状况下,可能存在不同的编辑功能。

更新日期:2020-07-20
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