Dimethyladenosine transferase 1 (DIMT1) is an evolutionarily conserved RNA N6,6-dimethyladenosine (m26,6A) methyltransferase. DIMT1 plays an important role in ribosome biogenesis, and the catalytic activity of DIMT1 is indispensable for cell viability and protein synthesis. A few RNA-modifying enzymes can install the same modification in multiple RNA species. However, whether DIMT1 can work on RNA species other than 18S rRNA is unclear. Here, we describe that DIMT1 generates m26,6A not only in 18S rRNA but also in small RNAs. In addition, m26,6A in small RNAs were significantly decreased in cells expressing catalytically inactive DIMT1 variants (E85A or NLPY variants) compared with cells expressing wildtype DIMT1. Both E85A and NLPY DIMT1 variant cells present decreased protein synthesis and cell viability. Furthermore, we observed that DIMT1 is highly expressed in human cancers, including acute myeloid leukemia. Our data suggest that downregulation of DIMT1 in acute myeloid leukemia cells leads to a decreased m26,6A level in small RNAs. Together, these data suggest that DIMT1 not only installs m26,6A in 18S rRNA but also generates m26,6A-containing small RNAs, both of which potentially contribute to the impact of DIMT1 on cell viability and gene expression.

中文翻译：

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人 DIMT1 生成含有 N26,6A-二甲基化的小 RNA。


二甲基腺苷转移酶 1 (DIMT1) 是一种进化上保守的 RNA N6,6-二甲基腺苷 (m26,6A) 甲基转移酶。 DIMT1在核糖体生物合成中发挥着重要作用，DIMT1的催化活性对于细胞活力和蛋白质合成是不可或缺的。一些 RNA 修饰酶可以在多种 RNA 中进行相同的修饰。然而，DIMT1 是否可以作用于 18S rRNA 以外的 RNA 种类尚不清楚。在这里，我们描述了 DIMT1 不仅在 18S rRNA 中生成 m26,6A，还在小 RNA 中生成 m26,6A。此外，与表达野生型 DIMT1 的细胞相比，在表达催化失活 DIMT1 变体（E85A 或 NLPY 变体）的细胞中，小 RNA 中的 m26,6A 显着减少。 E85A 和 NLPY DIMT1 变异细胞均表现出蛋白质合成和细胞活力下降。此外，我们观察到 DIMT1 在人类癌症中高表达，包括急性髓系白血病。我们的数据表明，急性髓系白血病细胞中 DIMT1 的下调导致小 RNA 中 m26,6A 水平降低。总之，这些数据表明 DIMT1 不仅在 18S rRNA 中安装 m26,6A，而且还生成含有 m26,6A 的小 RNA，这两者都可能有助于 DIMT1 对细胞活力和基因表达的影响。