Mark it for destruction: a novel role of mRNA methylation in maternal-to-zygotic transition†.
Mark it for destruction: a novel role of mRNA methylation in maternal-to-zygotic transition†.
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将其标记为破坏：mRNA 甲基化在母体向合子转变中的新作用。
DOI：
10.1093/biolre/iox016
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发表时间：
2017
影响因子：
3.6
通讯作者：
Yan,Wei
中科院分区：
文献类型：
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作者：
Yan,Wei
尽管在> 40年前首次报道了mRNA，如DNA，也含有甲基化碱基，特别是N6-甲基腺苷或m6 A [1]，但其可逆性[2]和m6 A的转录组范围映射最近才报道[3，4]。使用基于抗m6 A抗体的免疫沉淀，然后进行深度测序（m6 A-Seq），在哺乳动物细胞中已鉴定出由7000个基因编码的mRNA上的> 12000个潜在m6 A位点[3，4]。有趣的是，m6 A标记在mRNA上的非随机位置（例如，在3 '非翻译区（UTR）和终止密码子附近富集）表明该RNA标记可能在转录后调节中起作用。事实上，对m6 A作家的进一步研究（可以将甲基添加到腺苷的N6位的那些，例如，胃L3、胃L4和WTAP）和橡皮擦（可以去除甲基的那些，例如FTO和ALKBH 5），以及m6 A阅读器（特异性结合m6 A标记并触发下游细胞事件的那些，例如YTHDF和YTHDC家族），已经表明这些m6 A标记可以影响mRNA剪接、翻译状态和稳定性[5]。然而，这些影响主要是在体外培养的细胞中观察到的，缺乏m6 A writer，eraser和reader蛋白的动物模型的数据刚刚开始出现[6，7]。Chuan He实验室最近的一份报告[7]表明，斑马鱼中ythdf 2的失活，一种在卵母细胞和整个早期胚胎发育中大量表达的m6 A reader蛋白，导致在母体-合子转变（MZT）期间及时清除大部分母体转录物的显著延迟，并因此阻断单细胞胚胎中细胞周期的晚期G2至早期M期。通过使用mRNASeq分析mRNA和使用m6 A-CLIP-Seq定位m6 A位点，在> 40%的基因转录物（11631个中的4600个）中发现了m6 A峰，并且> 36%的母体转录物似乎含有m6 A标记。
Although it was first reported> 40 years ago that mRNAs, like DNA, also contain methylated bases, specifically N6-methyadnosine, or m6A [1], its reversibility [2] and transcriptome-wide mapping of m6A were only reported recently [3, 4]. Using anti-m6A antibodybased immunoprecipitation followed by deep sequencing (m6A-Seq),> 12 000 potential m6A sites on mRNAs encoded by∼ 7000 genes have been identified in mammalian cells [3, 4]. Interestingly, the nonrandom location of m6A marks on mRNAs (eg, enrichment in 3’untranslated regions (UTRs) and near the stop codon) suggests that this RNA mark may have a role in post-transcriptional regulation. Indeed, further studies on the m6A writers (those that can add the methyl group to the N6 position of adenosine, eg, METTL3, METTL4, and WTAP) and erasers (those that can remove the methyl group, eg, FTO and ALKBH5), as well as m6A readers (those that bind specifically m6A marks and trigger downstream cellular events, eg, YTHDF and YTHDC families), have suggested that these m6A marks can affect mRNA splicing, translational status, and stability [5]. However, the effects were observed mainly in cultured cells in vitro, and data from animal models lacking the m6A writer, eraser, and reader proteins just started emerging [6, 7].A very recent report [7] by Chuan He’s lab has shown that inactivation of ythdf2 in zebrafish, a m6A reader protein abundantly expressed in oocytes and throughout early embryonic development, leads to a significant delay in timely clearance of a significant proportion of the maternal transcripts during maternal-to-zygotic transition (MZT), and consequently a block in late G2 to early M phases of the cell cycle in one-cell embryos. By profiling mRNAs using mRNASeq and mapping m6A sites using m6A-CLIP-Seq, m6A peaks were found in> 40% of gene transcripts (4600 out of 11631) and> 36% of the maternal transcripts appeared to contain m6A marks dur-