FTO, the first RNA demethylase discovered, mediates the demethylation of internal N⁶-methyladenosine (m⁶A) and N⁶, 2-O-dimethyladenosine (m⁶A_m) 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 m⁶A and cap m⁶A_m in mRNA, internal m⁶A in U6 RNA, internal and cap m⁶A_m in snRNAs, and N¹-methyladenosine (m¹A) in tRNA. FTO-mediated demethylation has a greater effect on the transcript levels of mRNAs possessing internal m⁶A than the ones with cap m⁶A_m in the tested cells. We also show that FTO can directly repress translation by catalyzing m¹A tRNA demethylation. Collectively, FTO-mediated RNA demethylation occurs to m⁶A and m⁶A_m in mRNA and snRNA as well as m¹A in tRNA.

FTO 是第一个被发现的 RNA 去甲基化酶，介导mRNA 5' 帽 +1 位置处的内部N ⁶ -甲基腺苷 (m ⁶ A) 和N ⁶ , 2- O-二甲基腺苷 (m ⁶ A _{m ) 去甲基化。}在这里，我们证明 FTO 的细胞分布在不同细胞系中是不同的，影响 FTO 与不同 RNA 底物的接触。我们发现FTO结合多种RNA，包括mRNA、snRNA和tRNA，并且可以使mRNA中的内部m ⁶ A和cap m ⁶ A _m 、 U6 RNA中的内部m 6 A、snRNA中的内部m ^{6 A m和cap m 6} A _m去甲基化和tRNA 中的N ¹ -甲基腺苷 (m ¹ A)。在测试细胞中， FTO 介导的去甲基化对具有内部 m ⁶ A的 mRNA 的转录水平的影响比具有帽 m ⁶ A _{m的 mRNA 的转录水平影响更大。}^{我们还表明，FTO 可以通过催化 m 1} A tRNA 去甲基化来直接抑制翻译。总的来说，FTO 介导的 RNA 去甲基化发生在 mRNA 和 snRNA 中的 m ⁶ A 和 m ⁶ A _m以及tRNA 中的m ^{1 A。}