Li L, Dai H, Nguyen AP, Hai R, Gu W. Influenza A Virus Utilizes Non-Canonical Cap-Snatching to Diversify Its mRNA/ncRNA. RNA. 2020;rna.073866.119.
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.
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