Wiedermannová Jana, Julius Christina, Yuzenkova Yulia
Medical School, NUBI, Newcastle University, Newcastle upon Tyne, UK.
Umeå University, Umeå, Sweden.
R Soc Open Sci. 2021 May 19;8(5):201979. doi: 10.1098/rsos.201979.
Recent years witnessed the discovery of ubiquitous and diverse 5'-end RNA cap-like modifications in prokaryotes as well as in eukaryotes. These non-canonical caps include metabolic cofactors, such as NAD/NADH, FAD, cell wall precursors UDP-GlcNAc, alarmones, e.g. dinucleotides polyphosphates, ADP-ribose and potentially other nucleoside derivatives. They are installed at the 5' position of RNA via template-dependent incorporation of nucleotide analogues as an initiation substrate by RNA polymerases. However, the discovery of NAD-capped processed RNAs in human cells suggests the existence of alternative post-transcriptional NC capping pathways. In this review, we compiled growing evidence for a number of these other mechanisms which produce various non-canonically capped RNAs and a growing repertoire of capping small molecules. Enzymes shown to be involved are ADP-ribose polymerases, glycohydrolases and tRNA synthetases, and may potentially include RNA 3'-phosphate cyclases, tRNA guanylyl transferases, RNA ligases and ribozymes. An emerging rich variety of capping molecules and enzymes suggests an unrecognized level of complexity of RNA metabolism.
近年来,人们发现原核生物和真核生物中普遍存在多样的5'-端RNA帽状修饰。这些非规范帽包括代谢辅因子,如NAD/NADH、FAD、细胞壁前体UDP-GlcNAc、警报素,如二核苷酸多磷酸、ADP-核糖以及潜在的其他核苷衍生物。它们通过RNA聚合酶将核苷酸类似物作为起始底物进行模板依赖性掺入,安装在RNA的5'位置。然而,在人类细胞中发现NAD加帽的加工RNA表明存在替代性的转录后非规范加帽途径。在这篇综述中,我们收集了越来越多的证据,证明存在多种产生各种非规范加帽RNA的其他机制以及越来越多的加帽小分子。已证明涉及的酶有ADP-核糖聚合酶、糖水解酶和tRNA合成酶,可能还包括RNA 3'-磷酸环化酶、tRNA鸟苷酰转移酶、RNA连接酶和核酶。新出现的丰富多样的加帽分子和酶表明RNA代谢存在未被认识到的复杂程度。