5' End Nicotinamide Adenine Dinucleotide Cap in Human Cells Promotes RNA Decay through DXO-Mediated deNADding.
5' End Nicotinamide Adenine Dinucleotide Cap in Human Cells Promotes RNA Decay through DXO-Mediated deNADding.
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DOI：
10.1016/j.cell.2017.02.019
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发表时间：
2017-03-09
期刊：
影响因子：
64.5
通讯作者：
Kiledjian M
中科院分区：
文献类型：
--
作者：
Jiao X;Doamekpor SK;Bird JG;Nickels BE;Tong L;Hart RP;Kiledjian M
真核 mRNA 通常具有 5' 端 m7G 帽，可促进其翻译和稳定性。然而，哺乳动物 mRNA 也可以携带 5' 端烟酰胺腺嘌呤二核苷酸 (NAD+) 帽，与 m7G 帽相反，它不支持翻译，而是促进 mRNA 降解。哺乳动物和真菌的非经典 DXO/Rai1 脱帽酶可有效去除 DXO/Rai1 与 3'-NADP+ 的 NAD+ 帽和共晶结构，阐明了“deNADding”反应如何产生 NAD+ 和 5'-磷酸 RNA 的分子机制。从细胞中去除 DXO 会增加 NAD+ 加帽的 mRNA 水平，并能够检测 NAD+ 加帽的内含子 snoRNA，这表明 NAD+ 帽可以添加到 5' 加工的末端。我们的研究结果表明，NAD+ 是一种替代性哺乳动物 RNA 帽，DXO 是一种去 NAD 酶，可调节 NAD+ 帽 RNA 的细胞水平。总的来说，这些数据表明哺乳动物 RNA 可以含有与经典 m7G 帽不同的 5' 端修饰，从而促进而不是抑制 RNA 衰变。
Eukaryotic mRNAs generally possess a 5′-end m7G cap that promotes their translation and stability. However, mammalian mRNAs can also carry a 5′-end nicotinamide adenine dinucleotide (NAD+) cap that, in contrast to the m7G cap, does not support translation but instead promotes mRNA decay. The mammalian and fungal noncanonical DXO/Rai1 decapping enzymes efficiently remove NAD+ caps and cocrystal structures of DXO/Rai1 with 3′-NADP+ illuminates the molecular mechanism for how the “deNADding” reaction produces NAD+ and 5′-phosphate RNA. Removal of DXO from cells increases NAD+-capped mRNA levels and enables detection of NAD+-capped intronic snoRNAs, suggesting NAD+ caps can be added to 5′-processed termini. Our findings establish NAD+ as an alternative mammalian RNA cap and DXO as a deNADding enzyme modulating cellular levels of NAD+-capped RNAs. Collectively, these data reveal mammalian RNAs can harbor a 5′-end modification distinct from the classical m7G cap that promotes, rather than inhibits, RNA decay.