Identification of a novel deFADding activity in human, yeast and bacterial 5' to 3' exoribonucleases.
Identification of a novel deFADding activity in human, yeast and bacterial 5' to 3' exoribonucleases.
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DOI：
10.1093/nar/gkac617
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发表时间：
2022-08-26
影响因子：
14.9
通讯作者：
Kiledjian, Megerditch
中科院分区：
文献类型：
--
作者：
Sharma, Sunny;Yang, Jun;Doamekpor, Selom K.;Grudizen-Nogalska, Ewa;Tong, Liang;Kiledjian, Megerditch
对 RNA 5' 端包括 FAD 在内的代谢帽的鉴定揭示了细胞代谢和基因表达之间以前未预见到的交叉点。为了了解 FAD 帽在细胞生理学中的功能，我们表征了芽殖酵母中与 FAD 帽相互作用的蛋白质。在这里，我们证明高度保守的 5'-3' 核糖核酸外切酶 Xrn1 和 Rat1 与 RNA 5' FAD 帽发生物理相互作用，并且都具有 FAD 帽脱帽 (deFADding) 活性，随后降解所得 RNA。 Xrn1 deFADding 活性在人类细胞中也很明显，表明其进化保守性。此外，我们报告最近鉴定的细菌 5'-3' 核糖核酸外切酶 RNase AM 还具有 deFADding 活性，可以在体外和大肠杆菌细胞中降解 FAD 加帽的 RNA。为了获得对 deFADding 反应的分子理解，生成了由硫酸盐分子和活性位点氨基酸协调的三个锰离子的 RNase AM 晶体结构，该结构提供了 FAD 帽水解的详细信息。我们的研究结果揭示了 5'-3' 核糖核酸外切酶水解和降解具有 5' 末端非规范帽的 RNA 的一般倾向，以及其充分表征的 5' 单磷酸 RNA 底物，表明 5'-3' 核糖核酸外切酶的固有特性。
Identification of metabolite caps including FAD on the 5′ end of RNA has uncovered a previously unforeseen intersection between cellular metabolism and gene expression. To understand the function of FAD caps in cellular physiology, we characterised the proteins interacting with FAD caps in budding yeast. Here we demonstrate that highly conserved 5′-3′ exoribonucleases, Xrn1 and Rat1, physically interact with the RNA 5′ FAD cap and both possess FAD cap decapping (deFADding) activity and subsequently degrade the resulting RNA. Xrn1 deFADding activity was also evident in human cells indicating its evolutionary conservation. Furthermore, we report that the recently identified bacterial 5′-3′ exoribonuclease RNase AM also possesses deFADding activity that can degrade FAD-capped RNAs in vitro and in Escherichia coli cells. To gain a molecular understanding of the deFADding reaction, an RNase AM crystal structure with three manganese ions coordinated by a sulfate molecule and the active site amino acids was generated that provided details underlying hydrolysis of the FAD cap. Our findings reveal a general propensity for 5′-3′ exoribonucleases to hydrolyse and degrade RNAs with 5′ end noncanonical caps in addition to their well characterized 5′ monophosphate RNA substrates indicating an intrinsic property of 5′-3′ exoribonucleases.
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影响因子：
16.6
作者：
Sharma S;Yang J;Grudzien-Nogalska E;Shivas J;Kwan KY;Kiledjian M
通讯作者：
Kiledjian M
影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
DOI：
10.2183/pjab.91.394
发表时间：
2015
期刊：
Proceedings of the Japan Academy. Series B, Physical and biological sciences
影响因子：
--
作者：
Furuichi Y
通讯作者：
Furuichi Y
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
3.5
作者：
LARIMER, FW;HSU, CL;STEVENS, A
通讯作者：
STEVENS, A