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N6-甲基腺苷抑制局部核糖核酸内切酶切割以稳定拟南芥中的 mRNAs。

N-Methyladenosine Inhibits Local Ribonucleolytic Cleavage to Stabilize mRNAs in Arabidopsis.

机构信息

Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.

Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA; Cell and Molecular Biology Graduate Group, University of Pennsylvania, Philadelphia, PA 19104, USA.

出版信息

Cell Rep. 2018 Oct 30;25(5):1146-1157.e3. doi: 10.1016/j.celrep.2018.10.020.

Abstract

N-methyladenosine (mA) is a dynamic, reversible, covalently modified ribonucleotide that occurs predominantly toward 3' ends of eukaryotic mRNAs and is essential for their proper function and regulation. In Arabidopsis thaliana, many RNAs contain at least one mA site, yet the transcriptome-wide function of mA remains mostly unknown. Here, we show that many mA-modified mRNAs in Arabidopsis have reduced abundance in the absence of this mark. The decrease in abundance is due to transcript destabilization caused by cleavage occurring 4 or 5 nt directly upstream of unmodified mA sites. Importantly, we also find that, upon agriculturally relevant salt treatment, mA is dynamically deposited on and stabilizes transcripts encoding proteins required for salt and osmotic stress response. Overall, our findings reveal that mA generally acts as a stabilizing mark through inhibition of site-specific cleavage in plant transcriptomes, and this mechanism is required for proper regulation of the salt-stress-responsive transcriptome.

摘要

N6-甲基腺苷(m6A)是一种动态的、可逆的、共价修饰的核苷酸,主要出现在真核生物 mRNA 的 3' 端,对其正常功能和调控至关重要。在拟南芥中,许多 RNA 至少含有一个 m6A 位点,但 m6A 在转录组水平上的功能仍知之甚少。在这里,我们发现拟南芥中许多被 m6A 修饰的 mRNA 在没有这种修饰的情况下丰度降低。丰度的降低是由于在未修饰的 m6A 位点上游 4 或 5 个核苷酸处发生切割导致转录本不稳定。重要的是,我们还发现,在农业相关的盐处理下,m6A 会动态地被添加到编码盐和渗透胁迫反应所需蛋白的转录本上,并稳定这些转录本。总的来说,我们的研究结果表明,m6A 通常通过抑制植物转录组中特定位点的切割来发挥稳定作用,这种机制对于盐胁迫反应转录组的正确调控是必需的。

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