University of Chinese Academy of Sciences, Beijing 100049, China.
Shanxi Provincial Key Laboratory of Protein Structure Determination, Shanxi Academy of Advanced Research and Innovation, Taiyuan 030012, China.
Int J Mol Sci. 2023 Aug 9;24(16):12593. doi: 10.3390/ijms241612593.
Gene expression in eukaryotes begins with transcription in the nucleus, followed by the synthesis of messenger RNA (mRNA), which is then exported to the cytoplasm for its translation into proteins. Along with transcription and translation, mRNA export through the nuclear pore complex (NPC) is an essential regulatory step in eukaryotic gene expression. Multiple factors regulate mRNA export and hence gene expression. Interestingly, proteins from certain types of viruses interact with these factors in infected cells, and such an interaction interferes with the mRNA export of the host cell in favor of viral RNA export. Thus, these viruses hijack the host mRNA nuclear export mechanism, leading to a reduction in host gene expression and the downregulation of immune/antiviral responses. On the other hand, the viral mRNAs successfully evade the host surveillance system and are efficiently exported from the nucleus to the cytoplasm for translation, which enables the continuation of the virus life cycle. Here, we present this review to summarize the mechanisms by which viruses suppress host mRNA nuclear export during infection, as well as the key strategies that viruses use to facilitate their mRNA nuclear export. These studies have revealed new potential antivirals that may be used to inhibit viral mRNA transport and enhance host mRNA nuclear export, thereby promoting host gene expression and immune responses.
真核生物的基因表达始于细胞核中的转录,随后合成信使 RNA(mRNA),然后将其输出到细胞质中进行翻译为蛋白质。与转录和翻译一样,mRNA 通过核孔复合物(NPC)的输出是真核基因表达的一个重要调节步骤。多种因素调节 mRNA 输出,从而调节基因表达。有趣的是,某些类型的病毒的蛋白质在感染细胞中与这些因子相互作用,这种相互作用干扰宿主细胞的 mRNA 输出,有利于病毒 RNA 的输出。因此,这些病毒劫持了宿主的 mRNA 核输出机制,导致宿主基因表达减少和免疫/抗病毒反应下调。另一方面,病毒的 mRNA 成功地逃避了宿主的监控系统,并从细胞核有效地输出到细胞质中进行翻译,从而使病毒的生命周期得以继续。在这里,我们总结了病毒在感染过程中抑制宿主 mRNA 核输出的机制,以及病毒用来促进其 mRNA 核输出的关键策略。这些研究揭示了新的潜在抗病毒药物,这些药物可能被用于抑制病毒 mRNA 运输并促进宿主 mRNA 核输出,从而促进宿主基因表达和免疫反应。