Team R2D2: Retroviral RNA Dynamics and Delivery, IRIM, UMR9004, CNRS, University of Montpellier, Montpellier, FranceG.
RNA Biol. 2020 Apr;17(4):528-538. doi: 10.1080/15476286.2020.1713539. Epub 2020 Jan 23.
Cellular mRNAs are exported from the nucleus as fully spliced RNAs. Proofreading mechanisms eliminate unprocessed and irregular pre-mRNAs to control the quality of gene expression. Retroviruses need to export partially spliced and unspliced full-length RNAs to the cytoplasm where they serve as templates for protein synthesis and/or as encapsidated RNA in progeny viruses. Genetically complex retroviruses such as HIV-1 use Rev-equivalent proteins to export intron-retaining RNA from the nucleus using the cellular CRM1-driven nuclear export machinery. By contrast, genetically simpler retroviruses such as murine leukaemia virus (MLV) recruit the NXF1 RNA export machinery. In this study, we reveal for the first time that MLV hijacks both NXF1 and CRM1-dependent pathways to achieve optimal replication capacity. The CRM1-pathway marks the MLV full-length RNA (FL RNA) for packaging, while NXF1-driven nuclear export is coupled to translation. Thus, the cytoplasmic function of the viral RNA is determined early in the nucleus. Depending on the nature of ribonucleoprotein complex formed on FL RNA cargo in the nucleus, the FL RNA will be addressed to the translation machinery sites or to the virus-assembly sites at the plasma membrane.
细胞 mRNA 作为完全剪接的 RNA 从细胞核输出。校对机制消除未加工和不规则的前体 mRNA，以控制基因表达的质量。逆转录病毒需要将部分剪接和未剪接的全长 RNA 输出到细胞质，在那里它们作为蛋白质合成的模板和/或作为子代病毒的囊封 RNA。HIV-1 等遗传复杂的逆转录病毒使用 Rev 等效蛋白，利用细胞 CRM1 驱动的核输出机制从细胞核输出保留内含子的 RNA。相比之下，遗传上更简单的逆转录病毒，如鼠白血病病毒（MLV），招募 NXF1 RNA 输出机制。在这项研究中，我们首次揭示 MLV 劫持 NXF1 和 CRM1 依赖途径以实现最佳复制能力。CRM1 途径标记 MLV 全长 RNA (FL RNA) 进行包装，而 NXF1 驱动的核输出与翻译偶联。因此，病毒 RNA 的细胞质功能在细胞核中很早就被确定。根据核内 FL RNA 货物上形成的核糖核蛋白复合物的性质，FL RNA 将被靶向翻译机器位点或质膜上的病毒组装位点。
