DXO/Rai1 enzymes remove 5′-end FAD and dephospho-CoA caps on RNAs
DXO/Rai1 enzymes remove 5′-end FAD and dephospho-CoA caps on RNAs
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DOI：
10.1093/nar/gkaa297
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发表时间：
2020-06-19
影响因子：
14.9
通讯作者：
Tong, Liang
中科院分区：
文献类型：
--
作者：
Doamekpor, Selom K.;Grudzien-Nogalska, Ewa;Tong, Liang
在真核生物中，DXO/Rai1酶可以通过脱帽、denadd和焦磷酸水解酶活性消除大部分不完整和非规范的NAD帽。在这里，我们报道了这些酶也可以从RNA中去除FAD和去磷辅酶a （dpCoA）非规范帽，我们将这些活性命名为deFADding和deCoAping。哺乳动物DXO与3′-FADP或CoA的晶体结构以及裂变酵母ra1与3′-FADP的晶体结构为这些活动提供了优雅的见解。FAD和CoA通过折叠构象被安置在DXO/Rai1活性位点。FAD的黄素和CoA的泛茶氨酸基团在活性位点隧道底部接触同一区域，该区域发生构象变化以适应不同的帽基。我们已经开发了FAD- capq来检测和量化FAD帽盖rna，并确定人类细胞中的短rna（少于200个核苷酸）上存在FAD帽盖，并且这些rna在没有DXO的情况下是稳定的。
In eukaryotes, the DXO/Rai1 enzymes can eliminate most of the incomplete and non-canonical NAD caps through their decapping, deNADding and pyrophosphohydrolase activities. Here, we report that these enzymes can also remove FAD and dephospho-CoA (dpCoA) non-canonical caps from RNA, and we have named these activities deFADding and deCoAping. The crystal structures of mammalian DXO with 3'-FADP or CoA and fission yeast Rai1 with 3'-FADP provide elegant insight to these activities. FAD and CoA are accommodated in the DXO/Rai1 active site by adopting folded conformations. The flavin of FAD and the pantetheine group of CoA contact the same region at the bottom of the active site tunnel, which undergoes conformational changes to accommodate the different cap moieties. We have developed FAD-capQ to detect and quantify FAD-capped RNAs and determined that FAD caps are present on short RNAs (with less than similar to 200 nucleotides) in human cells and that these RNAs are stabilized in the absence of DXO.