Centre for Bacterial Cell Biology, Newcastle University, Newcastle upon Tyne, UK.
Wiley Interdiscip Rev RNA. 2019 Mar;10(2):e1512. doi: 10.1002/wrna.1512. Epub 2018 Oct 23.
Recently a new type of 5'-RNA cap was discovered. In contrast to the specialized eukaryotic m G cap, the novel caps are abundant cellular cofactors like NAD . RNAs capped with cofactors are found in prokaryotes and eukaryotes. Unlike m 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 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.
最近发现了一种新型的 5'-RNA 帽。与专门的真核 m G 帽不同，新型帽是 NAD 等丰富的细胞辅因子。带有辅因子的 RNA 存在于原核生物和真核生物中。与由专门的酶安装的 m G 帽不同，辅因子是由转录的主要酶，RNA 聚合酶（RNAP）连接的。辅因子作为非典型起始底物，在转录起始位点，辅因子的核苷碱基与模板 DNA 配对。含腺苷的 NAD（H）、黄素腺嘌呤二核苷酸（FAD）和 CoA 在以+1A 起始的启动子上修饰转录本。类似地，含尿苷的细胞壁前体，例如尿苷二磷酸-N-乙酰葡萄糖胺，已被证明在体外以+1U 启动子上帽 RNA。非典型加帽是进化上无关的 RNAP-多亚基细菌和真核 RNAP 以及单亚基线粒体 RNAP 的普遍特征。例如，NAD（H）等辅因子的细胞浓度明显高于转录中的 K。然而，只有一小部分给定的细胞 RNA 是非典型加帽的（如果有的话）。这一比例是加帽、看似随机的和脱帽、可能由 RNA 折叠、蛋白质结合和转录速率决定的净平衡。细菌和真核生物中的 NUDIX 水解酶和真核生物中的 DXO 家族蛋白作为非典型帽的脱帽酶。非典型 RNA 加帽的生理作用才刚刚开始显现。它被证明在细菌和真核生物中影响体内 RNA 的稳定性，并在体外刺激大肠杆菌中的 RNAP 启动子逃避。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，非典型加帽会影响 mRNA 翻译、RNA-蛋白质结合和 RNA 定位。本文归类于：RNA 加工>加帽和 5'端修饰 RNA 输出和定位>RNA 定位 RNA 结构和动态>RNA 结构、动态和化学。
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