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RNA 病毒 3'UTR 在 mRNA 稳定性和翻译增强中的作用。

The Role of 3'UTR of RNA Viruses on mRNA Stability and Translation Enhancement.

机构信息

Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Department of Virology, Pasteur Institute of Iran, Tehran, Iran.

出版信息

Mini Rev Med Chem. 2021;21(16):2389-2398. doi: 10.2174/1389557521666210217092305.

Abstract

The central dogma of molecular biology explains the flow of genetic information from DNA to functional products such as proteins. In most cases, a linear relationship with a high correlation coefficient exists between the concentration of mRNA, the middle man, and the functional product. Untranslated regions (UTRs) of RNA form a considerable base pairing that contributes to the secondary and tertiary structures of mRNA. The interaction between the mRNA secondary structures (cis-elements), RNA-binding proteins (RBP) and miRs (trans-element) are critical determinants of mRNAs' fate and stability. Among different viral families, the positive sense (+) RNA viruses use the simplest possible strategy of replication and expression, as the same molecule functions both as a genome and mRNA. Additionally, nucleotide composition and codon usage of +RNA viruses are the closest to human codon adaptation index (CAI). Since the origin of replication of viral intermediate RNA molecules is at the 3'-end of the genome, the 3'UTR plays a role in viral RNA replication. Moreover, the messenger role of RNA likely places functional demands on the 3'UTR to serve a role typical of cellular mRNA. This article reviews the effect of 3'UTR of RNA viruses with positive sense and genomes on mRNA stability and translation improvement. A range of animal (e.g., Dengue, Sindbis, Corona and Polio) and plant (Barley yellow dwarf, Brome mosaic, Turnip crinkle, Tobacco mosaic, Cowpea mosaic and Alfalfa mosaic) viruses are examined to highlight the role of 3'UTR in viral survival and as a potential target for pharmaceutical applications.

摘要

分子生物学的中心法则解释了遗传信息从 DNA 到功能性产物(如蛋白质)的流动。在大多数情况下,mRNA(中间产物)的浓度与功能性产物之间存在线性关系,且相关性很高。RNA 的非翻译区(UTR)形成了相当大的碱基配对,有助于 mRNA 的二级和三级结构。mRNA 二级结构(顺式元件)、RNA 结合蛋白(RBP)和 miRs(反式元件)之间的相互作用是决定 mRNA 命运和稳定性的关键决定因素。在不同的病毒家族中,正链(+)RNA 病毒采用最简单的复制和表达策略,因为同一分子既作为基因组又作为 mRNA 发挥作用。此外,+RNA 病毒的核苷酸组成和密码子使用最接近人类密码子适应指数(CAI)。由于病毒中间 RNA 分子的复制起点位于基因组的 3' 端,因此 3'UTR 在病毒 RNA 复制中发挥作用。此外,RNA 的信使作用可能对 3'UTR 提出了功能要求,使其能够发挥典型的细胞 mRNA 作用。本文综述了正链 RNA 病毒和基因组的 3'UTR 对 mRNA 稳定性和翻译改善的影响。检查了一系列动物(例如登革热、辛德比斯、冠状病毒和脊髓灰质炎)和植物(大麦黄矮、雀麦花叶、萝卜皱缩、烟草花叶、豇豆花叶和苜蓿花叶)病毒,以突出 3'UTR 在病毒存活中的作用以及作为药物应用的潜在靶点。

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