Xrn1 is a deNADding enzyme modulating mitochondrial NAD-capped RNA.
Xrn1 is a deNADding enzyme modulating mitochondrial NAD-capped RNA.
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DOI：
10.1038/s41467-022-28555-7
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发表时间：
2022-02-16
影响因子：
16.6
通讯作者：
Kiledjian M
中科院分区：
文献类型：
--
作者：
Sharma S;Yang J;Grudzien-Nogalska E;Shivas J;Kwan KY;Kiledjian M
非典型的烟酰胺腺嘌呤二磷酸（NAD）5′端加帽RNA的存在现在已经得到了很好的证实。然而，这种核苷酸代谢物帽的生物学功能仍然难以捉摸。在这里，我们表明，酵母酿酒酵母细胞质5′端核糖核酸外切酶Xrn 1也是一种NAD帽脱帽（deNADding）酶，释放完整的NAD，随后降解RNA。Xrn 1去NADding的重要性在去NADding缺陷型Xrn 1突变体中是明显的，该突变体主要仍然保留其5′-单磷酸核酸外切酶活性。该突变体揭示了Xrn 1 deNADding对于非发酵糖的正常生长是必需的，并且参与调节线粒体NAD加帽RNA水平，并且可能影响线粒体内NAD水平。我们的研究结果揭示了线粒体NAD加帽RNA在总体NAD调节中的贡献，其中Xrn 1的deNADding活性发挥了核心作用。胞质Xrn 1蛋白长期以来被确定为主要的5′至3′核糖核酸外切酶，其切割具有未保护的5′单磷酸末端的RNA。在这里，作者证明了Xrn 1也可以通过去除NAD帽并降解RNA来降解含有非经典烟酰胺腺嘌呤二磷酸（NAD）5′帽的RNA。
The existence of non-canonical nicotinamide adenine diphosphate (NAD) 5′-end capped RNAs is now well established. Nevertheless, the biological function of this nucleotide metabolite cap remains elusive. Here, we show that the yeast Saccharomyces cerevisiae cytoplasmic 5′-end exoribonuclease Xrn1 is also a NAD cap decapping (deNADding) enzyme that releases intact NAD and subsequently degrades the RNA. The significance of Xrn1 deNADding is evident in a deNADding deficient Xrn1 mutant that predominantly still retains its 5′-monophosphate exonuclease activity. This mutant reveals Xrn1 deNADding is necessary for normal growth on non-fermenting sugar and is involved in modulating mitochondrial NAD-capped RNA levels and may influence intramitochondrial NAD levels. Our findings uncover a contribution of mitochondrial NAD-capped RNAs in overall NAD regulation with the deNADding activity of Xrn1 fulfilling a central role. The cytoplasmic Xrn1 protein has long been established as the predominate 5′ to 3′ exoribonuclease that cleaves RNAs with an unprotected 5′ monophosphate end. Here the authors demonstrate Xrn1 can also degrade RNAs harboring the noncanonical nicotinamide adenine diphosphate (NAD) 5′ cap by removing the NAD cap and degrading the RNA.
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DOI：
10.1261/rna.060541.116
发表时间：
2017-05
期刊：
RNA (New York, N.Y.)
影响因子：
--
作者：
Celik A;Baker R;He F;Jacobson A
通讯作者：
Jacobson A
影响因子：
7.7
作者：
Bird, Jeremy G.;Basu, Urmimala;Nickels, Bryce E.
通讯作者：
Nickels, Bryce E.
影响因子：
11.4
作者：
Dehecq, Marine;Decourty, Laurence;Saveanu, Cosmin
通讯作者：
Saveanu, Cosmin
影响因子：
64.5
作者：
Jiao X;Doamekpor SK;Bird JG;Nickels BE;Tong L;Hart RP;Kiledjian M
通讯作者：
Kiledjian M
影响因子：
16
作者：
Jinek M;Coyle SM;Doudna JA
通讯作者：
Doudna JA