m6A甲基化在围产期的作用

Kosuke Taniguchi, T. Kawai
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引用次数: 0

摘要

n6 -甲基腺苷(N6-methyladenosine, m6A)是信使RNA (mRNA)和长链非编码RNA的主要修饰物,在RNA代谢和功能[1]中起关键作用。在众多的RNA修饰类型中,m6A是最常见和最丰富的化学转录后RNA修饰[2]。甲基化RNA免疫沉淀测序(MeRIP-Seq)是一种确定m6A[1]存在的综合检测方法。自本实验发展以来,m6A的功能逐渐清晰,编码mRNA中的m6A在停止密码子附近最为丰富,特别是在3'UTR内,它们具有一致的RRACH序列,其中R是嘌呤,H是除G[1]以外的任何碱基。m6A参与转录后调控,特别是决定mRNA[3]的稳定性和寿命。此外,已经报道了几种m6A调节因子,如甲基化酶m6A写入蛋白(METTL3, METTL14, METTL16, WTAP),去甲基化酶m6A擦除蛋白(FTO, ALKBH5)和识别m6A[3]的m6A读取蛋白(YTH家族)。同一基因mRNA中m6A位点在不同细胞和组织类型中存在差异;m6A水平在外界刺激下发生变化,从而作为一种动态修饰,微调基因表达[4]。值得注意的是,虽然mRNA(由基因表达产生)和蛋白质的水平呈正相关,但相关性很弱;这并不是一个完美的相关性。因此,通过m6A修饰阐明转录后mRNA调控有助于阐明参与各种细胞事件的基因的作用。
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m6A methylation in the perinatal field
N6-methyladenosine (m6A), a major modification of messenger RNA (mRNA) and long non-coding RNA, plays critical roles in RNA metabolism and function [1]. Among the many types of RNA modification, m6A is the most frequent and abundant chemical post-transcriptional RNA modification [2]. Methylated RNA immunoprecipitation followed by sequencing (MeRIP-Seq) is a comprehensive assay to determine the presence of m6A [1]. Since the development of this assay, the functions of m6A have gradually become clearer m6A within coding mRNA are most abundantly observed in the vicinity of the stop codon, especially within the 3'UTR, and they have a consensus sequence of RRACH, where R is a purine and H is any base except for G [1]. m6A is involved in post-transcriptional regulation, especially in determining the stability and lifespan of mRNA [3]. Furthermore, several m6A regulators have been reported, such as the methylating enzyme m6A writer proteins (METTL3, METTL14, METTL16, WTAP), the demethylating enzyme m6A eraser proteins (FTO, ALKBH5), and m6A reader proteins (YTH family) that recognize m6A [3]. The m6A site in mRNA of the same gene differs between cell and tissue types; m6A levels change in response to external stimuli, thereby functioning as a dynamic type of modification that fine-tunes gene expression [4]. Notably, although the levels of mRNA (arising from gene expression) and protein are positively correlated, the correlation is weak; it is not a perfect correlation [5]. Therefore, elucidation of post-transcriptional mRNA regulation through m6A modifications can help clarify the role of genes involved in various cellular events.
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