剪接位点 mA 甲基化阻止 U2AF35 结合，从而抑制 RNA 剪接。
Splice site mA methylation prevents binding of U2AF35 to inhibit RNA splicing.
机构信息
Department of Molecular Biology, Science III, University of Geneva, 30 Quai Ernest-Ansermet, 1211 Geneva 4, Switzerland.
Proteomics and Modomics Experimental Core (PROMEC), Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU) and St. Olavs Hospital Central Staff, Trondheim, Norway.
出版信息
Cell. 2021 Jun 10;184(12):3125-3142.e25. doi: 10.1016/j.cell.2021.03.062. Epub 2021 Apr 29.
The N-methyladenosine (mA) RNA modification is used widely to alter the fate of mRNAs. Here we demonstrate that the C. elegans writer METT-10 (the ortholog of mouse METTL16) deposits an mA mark on the 3' splice site (AG) of the S-adenosylmethionine (SAM) synthetase pre-mRNA, which inhibits its proper splicing and protein production. The mechanism is triggered by a rich diet and acts as an mA-mediated switch to stop SAM production and regulate its homeostasis. Although the mammalian SAM synthetase pre-mRNA is not regulated via this mechanism, we show that splicing inhibition by 3' splice site mA is conserved in mammals. The modification functions by physically preventing the essential splicing factor U2AF35 from recognizing the 3' splice site. We propose that use of splice-site mA is an ancient mechanism for splicing regulation.
N6-甲基腺苷（m6A）RNA 修饰被广泛用于改变 mRNA 的命运。在这里，我们证明秀丽隐杆线虫的 writer METT-10（对应于小鼠 METTL16）在 S-腺苷甲硫氨酸（SAM）合成酶前体 mRNA 的 3' 剪接位点（AG）上沉积 mA 标记，这抑制了其正确的剪接和蛋白质产生。该机制是由丰富的饮食触发的，作为一种 mA 介导的开关，以停止 SAM 的产生并调节其体内平衡。尽管哺乳动物的 SAM 合成酶前体 mRNA 不受此机制调控，但我们表明，3' 剪接位点 mA 的剪接抑制在哺乳动物中是保守的。这种修饰通过物理上阻止必需的剪接因子 U2AF35 识别 3' 剪接位点来发挥作用。我们提出，使用剪接位点 mA 是一种古老的剪接调控机制。
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