From the Department of Chemistry and Biochemistry, Center for Retrovirus Research, and Center for RNA Biology, The Ohio State University, Columbus, Ohio 43210.
From the Department of Chemistry and Biochemistry, Center for Retrovirus Research, and Center for RNA Biology, The Ohio State University, Columbus, Ohio 43210
J Biol Chem. 2019 Apr 5;294(14):5352-5364. doi: 10.1074/jbc.REV118.002957. Epub 2019 Jan 30.
The lifecycle of retroviruses and retrotransposons includes a reverse transcription step, wherein dsDNA is synthesized from genomic RNA for subsequent insertion into the host genome. Retroviruses and retrotransposons commonly appropriate major components of the host cell translational machinery, including cellular tRNAs, which are exploited as reverse transcription primers. Nonpriming functions of tRNAs have also been proposed, such as in HIV-1 virion assembly, and tRNA-derived fragments may also be involved in retrovirus and retrotransposon replication. Moreover, host cellular proteins regulate retroviral replication by binding to tRNAs and thereby affecting various steps in the viral lifecycle. For example, in some cases, tRNA primer selection is facilitated by cognate aminoacyl-tRNA synthetases (ARSs), which bind tRNAs and ligate them to their corresponding amino acids, but also have many known nontranslational functions. Multi-omic studies have revealed that ARSs interact with both viral proteins and RNAs and potentially regulate retroviral replication. Here, we review the currently known roles of tRNAs and their derivatives in retroviral and retrotransposon replication and shed light on the roles of tRNA-binding proteins such as ARSs in this process.
逆转录病毒和 retrotransposons 的生命周期包括逆转录步骤，其中双链 DNA 是从基因组 RNA 合成的，用于随后插入宿主基因组。逆转录病毒和 retrotransposons 通常采用宿主细胞翻译机制的主要成分，包括细胞 tRNAs，这些 tRNAs 被用作逆转录引物。tRNAs 的非引物功能也已经被提出，例如在 HIV-1 病毒粒子组装中，并且 tRNA 衍生的片段也可能参与逆转录病毒和 retrotransposon 的复制。此外，宿主细胞蛋白通过与 tRNAs 结合来调节逆转录病毒的复制，从而影响病毒生命周期的各个步骤。例如，在某些情况下，tRNA 引物的选择是由同源氨酰-tRNA 合成酶 (ARS) 促进的，ARS 结合 tRNAs 并将它们连接到相应的氨基酸上，但也具有许多已知的非翻译功能。多组学研究表明，ARSs 与病毒蛋白和 RNA 相互作用，并可能调节逆转录病毒的复制。在这里，我们综述了 tRNAs 及其衍生物在逆转录病毒和 retrotransposon 复制中的目前已知作用，并阐明了 tRNA 结合蛋白（如 ARS）在这一过程中的作用。
