With sizes <50 kb, viral RNA genomes are at the crossroads of genetic, biophysical, and biochemical stability in their host cell. Here, we analyze the enzymatic assets accompanying large RNA genome viruses, mostly based on recent scientific advances in Coronaviridae. We argue that, in addition to the presence of an RNA exonuclease (ExoN), two markers for the large size of viral RNA genomes are (i) the presence of one or more RNA methyltransferases (MTases) and (ii) a specific architecture of the RNA-dependent RNA polymerase active site. We propose that RNA genome expansion and maintenance are driven by an evolutionary ménage-à-trois made of fast and processive RNA polymerases, RNA repair ExoNs, and RNA MTases that relates to the transition between RNA- to DNA-based life.

病毒 RNA 基因组大小小于 50 kb，处于宿主细胞中遗传、生物物理和生化稳定性的十字路口。在这里，我们分析了伴随大型 RNA 基因组病毒的酶学资产，主要基于冠状病毒科的最新科学进展。我们认为，除了 RNA 外切核酸酶 (ExoN) 的存在外，病毒 RNA 基因组大尺寸的两个标记是 (i) 一种或多种 RNA 甲基转移酶 (MTase) 的存在和 (ii) RNA依赖的RNA聚合酶活性位点。我们提出 RNA 基因组的扩展和维护是由快速和持续的 RNA 聚合酶、RNA 修复 ExoN 和 RNA MTase 组成的进化ménage-à-trois驱动的，这与 RNA 到基于 DNA 的生命之间的过渡有关。