Noncanonical RNA-capping: Discovery, mechanism, and physiological role debate
Noncanonical RNA-capping: Discovery, mechanism, and physiological role debate
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DOI：
10.1002/wrna.1512
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发表时间：
2019-03-01
影响因子：
7.3
通讯作者：
Yuzenkova, Yulia
中科院分区：
文献类型：
--
作者：
Julius, Christina;Yuzenkova, Yulia
最近发现了一种新型的5 '-RNA帽。与专门的真核m（7）G帽相比，新的帽是丰富的细胞辅因子，如NAD（+）。在原核生物和真核生物中发现了用辅因子加帽的RNA。与m（7）G帽不同，辅因子由转录的主要酶RNA聚合酶（RNAP）连接。辅因子作为非典型的起始底物，在转录起始位点提供辅因子的核苷碱基对与模板DNA。含腺苷的NAD（H）、黄素腺嘌呤二核苷酸（FAD）和CoA修饰启动子上以+1A开始的转录物。类似地，含有尿苷的细胞壁前体，例如尿苷二磷酸-N-乙酰葡糖胺，显示出在体外将RNA加帽在+1U启动子上。非规范帽是一个普遍的功能，进化无关的RNAP-多亚基细菌和真核RNAP，和单亚基线粒体RNAP。辅因子（例如NAD（H））的细胞浓度显著高于它们在转录中的K-m。然而，只有一小部分给定的细胞RNA是非规范加帽的（如果有的话）。这个比例是一个净平衡之间的加盖，看似随机，和脱帽，可能由RNA折叠，蛋白质结合和转录速率。细菌和真核生物中的NUDIX水解酶以及真核生物中的DXO家族蛋白质充当非规范帽的去帽酶。非规范RNA加帽的生理作用才刚刚开始出现。它被证明在细菌和真核生物体内影响RNA稳定性，并在大肠杆菌体外刺激RNAP启动子逃逸。NAD（+）/NADH加帽比可能将转录与细胞氧化还原状态联系起来。潜在地，非规范加帽影响mRNA翻译、RNA-蛋白质结合和RNA定位。本文分类下：RNA加工>加帽和5 '端修饰RNA导出和定位> RNA定位RNA结构和动力学> RNA结构，动力学，和化学
Recently a new type of 5 '-RNA cap was discovered. In contrast to the specialized eukaryotic m(7)G cap, the novel caps are abundant cellular cofactors like NAD(+). RNAs capped with cofactors are found in prokaryotes and eukaryotes. Unlike m(7)G cap, installed by specialized enzymes, cofactors are attached by main enzyme of transcription, RNA polymerase (RNAP). Cofactors act as noncanonical initiating substrates, provided cofactor's nucleoside base-pairs with template DNA at the transcription start site. Adenosine-containing NAD(H), flavin adenine dinucleotide (FAD), and CoA modify transcripts on promoters starting with +1A. Similarly, uridine-containing cell wall precursors, for example, uridine diphosphate-N-acetylglucosamine were shown to cap RNA in vitro on +1U promoters. Noncanonical capping is a universal feature of evolutionary unrelated RNAPs-multisubunit bacterial and eukaryotic RNAPs, and single-subunit mitochondrial RNAP. Cellular concentrations of cofactors, for example, NAD(H) are significantly higher than their K-m in transcription. Yet, only a small proportion of a given cellular RNA is noncanonically capped (if at all). This proportion is a net balance between capping, seemingly stochastic, and decapping, possibly determined by RNA folding, protein binding and transcription rate. NUDIX hydrolases in bacteria and eukaryotes, and DXO family proteins eukaryotes act as decapping enzymes for noncanonical caps. The physiological role of noncanonical RNA capping is only starting to emerge. It was demonstrated to affect RNA stability in vivo in bacteria and eukaryotes and to stimulate RNAP promoter escape in vitro in Escherichia coli. NAD(+)/NADH capping ratio may connect transcription to cellular redox state. Potentially, noncanonical capping affects mRNA translation, RNA-protein binding and RNA localization. This article is categorized under: RNA Processing > Capping and 5 ' End Modifications RNA Export and Localization > RNA Localization RNA Structure and Dynamics > RNA Structure, Dynamics, and Chemistry