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SARS-CoV-2 突变导致肺部组织特异性 microRNA 结合区域数量减少。

SARS-CoV-2 Mutations Lead to a Decrease in the Number of Tissue-Specific MicroRNA-Binding Regions in the Lung.

机构信息

M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.

Faculty of Biology and Biotechnologies, Higher School of Economics (HSE University), Moscow, Russia.

出版信息

Bull Exp Biol Med. 2023 Feb;174(4):527-532. doi: 10.1007/s10517-023-05742-0. Epub 2023 Mar 11.

Abstract

RNA interference in vertebrates acts as an antiviral mechanism only in undifferentiated embryonic stem cells and is mediated by microRNAs. In somatic cells, host microRNAs also bind to the genomes of RNA viruses, regulating their translation and replication. It has been shown that viral (+)RNA can evolve under the influence of host cell miRNAs. In more than two years of the pandemic, the SARS-CoV-2 virus has mutated significantly. It is quite possible that some mutations could be retained in the virus genome under the influence of miRNAs produced by alveolar cells. We demonstrated that microRNAs in human lung tissue exert evolutionary pressure on the SARS-CoV-2 genome. Moreover, a significant number of sites of host microRNA binding with the virus genome are located in the NSP3-NSP5 region responsible for autoproteolysis of viral polypeptides.

摘要

脊椎动物中的 RNA 干扰仅作为一种抗病毒机制存在于未分化的胚胎干细胞中,并由 microRNAs 介导。在体细胞中,宿主 microRNAs 也能与 RNA 病毒的基因组结合,从而调节其翻译和复制。已经表明,病毒(+)RNA 可以在宿主细胞 microRNAs 的影响下进化。在大流行的两年多时间里,SARS-CoV-2 病毒发生了显著突变。很有可能一些突变可以在肺泡细胞产生的 microRNAs 的影响下保留在病毒基因组中。我们证明了人类肺组织中的 microRNAs 对 SARS-CoV-2 基因组施加了进化压力。此外,大量宿主 microRNA 与病毒基因组结合的位点位于 NSP3-NSP5 区域,该区域负责病毒多肽的自蛋白酶解。

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