RNA中6-甲基腺嘌呤的研究进展
收稿日期: 2013-04-28
修回日期: 2013-08-25
网络出版日期: 2013-11-21
基金资助
国家自然科学基金项目(编号：31271372)和北京市科技新星计划(编号：Z121105002512060)资助
Recent progresses in RNA N6-methyladenosine research
Received date: 2013-04-28
Revised date: 2013-08-25
Online published: 2013-11-21
RNA酶促共价修饰研究, 尤其是m6A(6-甲基腺嘌呤), 是RNA生物学研究的一个新兴领域。m6A是真核生物mRNA内部序列中最常见的一种转录后修饰形式, 由包含3个独立组分的复合物mRNA: m6A甲基转移酶催化生成。最新研究发现肥胖相关蛋白FTO可以脱掉m6A上的甲基, 表明该甲基化过程是可逆的。抑制或敲除m6A甲基转移酶会引起重要的表型变化, 但是由于过去的检测方法受限, m6A确切的作用机制目前为止还不甚清楚。二代测序技术结合免疫沉淀方法为大规模检测m6A修饰并研究其作用机制提供了可能。文章主要综述了m6A的发现史、生成机制、组织和基因组分布、检测方法、生物学功能等及其最新研究进展, 并通过比较3种IP-seq技术和数据分析的异同及优缺点, 对m6A这种RNA表观修饰研究中尚未解决的问题进行了讨论。
李语丽 于军 宋述慧 . RNA中6-甲基腺嘌呤的研究进展[J]. 遗传, 2013 , 35(12) : 1340 -1351 . DOI: 10.3724/SP.J.1005.2013.01340
RNA modifications, especially methylation of the N6 position of adenosine (A)––m6A, represent an emerging research territory in RNA biology. m6A is a post-transcriptional modification of RNAs, which is catalyzed by the mRNA: m6A methyltransferase complex containing three individual components and is the most common form found in the internal se-quences of mRNAs in eukaryotes. Latest study showed that the fat mass and obesity-associated protein could remove the methyl group, indicating that the modification is reversible. Importantly, inhibiting or silencing the methyltransferase will cause significant changes of phenotypes. However, due to limited detection methods, the mechanism of m6A has not been figured out yet. Next-generation sequencing combining with IP (immunoprecipitation) technologies makes it possible to detect m6A modifications in a large scale. Here, we reviewed recent progresses of m6A studies including the discovery of m6A, mechanism of biosynthesis, tissue and genome distribution, detection methodology and possible biological functions. We also compared three IP-seq technologies that are currently widely used, and summarized the challenges in m6A studies.
Key words： RNA modifications; m6A; IP-seq
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