Division of Biophysics, Institute of Experimental Physics, Faculty of Physics, University of Warsaw, Zwirki i Wigury 93, 02-089, Warsaw, Poland.
Centre of New Technologies, University of Warsaw, Banacha 2c, 02-097, Warsaw, Poland.
Top Curr Chem (Cham). 2017 Feb;375(1):16. doi: 10.1007/s41061-017-0106-y. Epub 2017 Jan 23.
The cap is a natural modification present at the 5' ends of eukaryotic messenger RNA (mRNA), which because of its unique structural features, mediates essential biological functions during the process of gene expression. The core structural feature of the mRNA cap is an N7-methylguanosine moiety linked by a 5'-5' triphosphate chain to the first transcribed nucleotide. Interestingly, other RNA 5' end modifications structurally and functionally resembling the mG cap have been discovered in different RNA types and in different organisms. All these structures contain the 'inverted' 5'-5' oligophosphate bridge, which is necessary for interaction with specific proteins and also serves as a cleavage site for phosphohydrolases regulating RNA turnover. Therefore, cap analogs containing oligophosphate chain modifications or carrying spectroscopic labels attached to phosphate moieties serve as attractive molecular tools for studies on RNA metabolism and modification of natural RNA properties. Here, we review chemical, enzymatic, and chemoenzymatic approaches that enable preparation of modified cap structures and RNAs carrying such structures, with emphasis on phosphate-modified mRNA cap analogs and their potential applications.
帽子是真核信使 RNA（mRNA）5'端的一种天然修饰，由于其独特的结构特征，在基因表达过程中介导重要的生物学功能。mRNA 帽子的核心结构特征是通过 5'-5'三磷酸链连接到第一个转录核苷酸的 N7-甲基鸟苷部分。有趣的是，在不同的 RNA 类型和不同的生物体中，已经发现了其他结构和功能类似于 mG 帽子的其他 RNA 5'端修饰。所有这些结构都包含“反向”5'-5'寡聚磷酸桥，这对于与特定蛋白质的相互作用是必要的，并且也作为调节 RNA 周转的磷酸水解酶的切割位点。因此，含有寡聚磷酸链修饰的帽类似物或携带附着在磷酸部分的光谱标记物作为研究 RNA 代谢和修饰天然 RNA 性质的有吸引力的分子工具。在这里，我们综述了能够制备修饰的帽结构和携带这些结构的 RNA 的化学、酶和化学酶方法，重点介绍了磷酸修饰的 mRNA 帽类似物及其潜在应用。
