FTO 在细胞核和细胞质中介导的差异 mA、mA 和 mA 去甲基化。
Differential mA, mA, and mA Demethylation Mediated by FTO in the Cell Nucleus and Cytoplasm.
机构信息
Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57 Street, Chicago, IL 60637, USA; Howard Hughes Medical Institute, The University of Chicago, 929 East 57 Street, Chicago, IL 60637, USA.
Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57 Street, Chicago, IL 60637, USA; Howard Hughes Medical Institute, The University of Chicago, 929 East 57 Street, Chicago, IL 60637, USA; Institute of Natural Sciences, Westlake Institute for Advanced Study, Westlake University, 18 Shilongshan Road, Hangzhou 310064, China.
出版信息
Mol Cell. 2018 Sep 20;71(6):973-985.e5. doi: 10.1016/j.molcel.2018.08.011. Epub 2018 Sep 6.
FTO, the first RNA demethylase discovered, mediates the demethylation of internal N-methyladenosine (mA) and N, 2-O-dimethyladenosine (mA) at the +1 position from the 5' cap in mRNA. Here we demonstrate that the cellular distribution of FTO is distinct among different cell lines, affecting the access of FTO to different RNA substrates. We find that FTO binds multiple RNA species, including mRNA, snRNA, and tRNA, and can demethylate internal mA and cap mA in mRNA, internal mA in U6 RNA, internal and cap mA in snRNAs, and N-methyladenosine (mA) in tRNA. FTO-mediated demethylation has a greater effect on the transcript levels of mRNAs possessing internal mA than the ones with cap mA in the tested cells. We also show that FTO can directly repress translation by catalyzing mA tRNA demethylation. Collectively, FTO-mediated RNA demethylation occurs to mA and mA in mRNA and snRNA as well as mA in tRNA.
FTO 是首个被发现的 RNA 去甲基酶，可介导 mRNA 5' 帽位+1 位内部 N6-甲基腺苷（m6A）和 N6,2-O-二甲基腺苷（m6Am）的去甲基化。在此，我们证明了 FTO 在不同细胞系中的细胞分布不同，影响 FTO 对不同 RNA 底物的接近。我们发现 FTO 可结合多种 RNA 种类，包括 mRNA、snRNA 和 tRNA，并且可使 mRNA 中的内部 m6A 和帽 m6A、U6 RNA 中的内部 m6A、snRNA 中的内部和帽 m6A 以及 tRNA 中的 N6-甲基腺苷（m6A）去甲基化。在测试的细胞中，FTO 介导的去甲基化对具有内部 m6A 的 mRNA 的转录水平的影响大于具有帽 m6A 的 mRNA。我们还表明，FTO 可通过催化 m6A-tRNA 去甲基化直接抑制翻译。总的来说，FTO 介导的 RNA 去甲基化发生在 mRNA 和 snRNA 中的 m6A 和 m6Am 以及 tRNA 中的 m6A。
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