Influenza A virus (IAV) utilizes cap-snatching to obtain host capped small RNAs for priming viral mRNA synthesis, generating capped hybrid mRNAs for translation. Previous studies have been focusing on canonical cap-snatching, which occurs at the very 5' end of viral mRNAs. Here we discovered non-canonical cap-snatching, which generates capped hybrid mRNAs/noncoding RNAs mapped to the region ~300 nucleotides (nt) upstream of each mRNA 3' end, and to the 5' region, primarily starting at the second nt, of each virion RNAs (vRNA). Like canonical cap-snatching, non-canonical cap-snatching utilizes a base-pairing between the last nt G of host capped RNAs and a nt C of template RNAs to prime RNA synthesis. However, the nt upstream of this template C is usually A/U rather than just U; prime-realignment occurs less frequently. We also demonstrate that IAV can snatch capped IAV RNAs in addition to host RNAs. Non-canonical cap-snatching likely generates novel mRNAs with start AUG encoded in viral or host RNAs. These findings expand our understanding of cap-snatching mechanisms and suggest that IAV may utilize non-canonical cap-snatching to diversify its mRNAs/ncRNAs.

中文翻译：

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甲型流感病毒利用非规范帽抢夺来使其 mRNA/ncRNA 多样化

甲型流感病毒 (IAV) 利用抢帽获得宿主加帽的小 RNA 以启动病毒 mRNA 合成，生成加帽的杂交 mRNA 以进行翻译。以前的研究一直集中在规范的帽子抢夺上，它发生在病毒 mRNA 的 5' 末端。在这里，我们发现了非规范的帽子抢夺，它生成了加帽的混合 mRNA/非编码 RNA，这些 mRNA 映射到每个 mRNA 3' 末端上游约 300 个核苷酸 (nt) 的区域，以及 5' 区域，主要从第二个 nt 开始，每个病毒体 RNA (vRNA)。与规范的帽子抢夺一样，非规范的帽子抢夺利用宿主加帽 RNA 的最后一个 nt G 和模板 RNA 的 nt C 之间的碱基配对来启动 RNA 合成。但是，这个模板 C 的上游 nt 通常是 A/U 而不仅仅是 U；素数重排发生的频率较低。我们还证明，除了宿主 RNA 之外，IAV 还可以抢夺加帽的 IAV RNA。非规范的帽子抢夺可能会产生新的 mRNA，起始 AUG 编码在病毒或宿主 RNA 中。这些发现扩展了我们对 cap-snatching 机制的理解，并表明 IAV 可能利用非规范的 cap-snatching 使其 mRNAs/ncRNAs 多样化。