Department of Biochemistry and Molecular Biology, Southern Illinois University School of Medicine, Carbondale, IL 62901, USA.
Department of Biochemistry and Molecular Biology, Southern Illinois University School of Medicine, Carbondale, IL 62901, USA.
Biochim Biophys Acta Gene Regul Mech. 2021 Jan;1864(1):194655. doi: 10.1016/j.bbagrm.2020.194655. Epub 2020 Nov 24.
Eukaryotic gene expression begins with transcription in the nucleus to synthesize mRNA (messenger RNA), which is subsequently exported to the cytoplasm for translation to protein. Like transcription and translation, mRNA export is an important regulatory step of eukaryotic gene expression. Various factors are involved in regulating mRNA export, and thus gene expression. Intriguingly, some of these factors interact with viral proteins, and such interactions interfere with mRNA export of the host cell, favoring viral RNA export. Hence, viruses hijack host mRNA export machinery for export of their own RNAs from nucleus to cytoplasm for translation to proteins for viral life cycle, suppressing host mRNA export (and thus host gene expression and immune/antiviral response). Therefore, the molecules that can impair the interactions of these mRNA export factors with viral proteins could emerge as antiviral therapeutic agents to suppress viral RNA transport and enhance host mRNA export, thereby promoting host gene expression and immune response. Thus, there has been a number of studies to understand how virus hijacks mRNA export machinery in suppressing host gene expression and promoting its own RNA export to the cytoplasm for translation to proteins required for viral replication/assembly/life cycle towards developing targeted antiviral therapies, as concisely described here.
真核生物基因表达始于细胞核中的转录以合成 mRNA(信使 RNA),随后将其输出到细胞质中以翻译为蛋白质。与转录和翻译一样,mRNA 输出是真核生物基因表达的重要调节步骤。各种因素参与调节 mRNA 输出,从而调节基因表达。有趣的是,其中一些因素与病毒蛋白相互作用,这种相互作用会干扰宿主细胞的 mRNA 输出,有利于病毒 RNA 的输出。因此,病毒劫持宿主 mRNA 输出机制,将自身的 RNA 从细胞核输出到细胞质进行翻译以产生蛋白质,完成病毒生命周期,抑制宿主 mRNA 输出(从而抑制宿主基因表达和免疫/抗病毒反应)。因此,能够破坏这些 mRNA 输出因子与病毒蛋白相互作用的分子可能成为抗病毒治疗药物,以抑制病毒 RNA 转运并增强宿主 mRNA 输出,从而促进宿主基因表达和免疫反应。因此,已经有许多研究旨在了解病毒如何劫持 mRNA 输出机制来抑制宿主基因表达并促进自身 RNA 输出到细胞质进行翻译以产生蛋白质,以完成病毒复制/组装/生命周期,从而开发靶向抗病毒疗法,这里简要介绍一下。