Small RNA Plays Important Roles in Virus–Host Interactions

Figures

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  Figure 1. Canonical cap-snatching. (A) IAV mRNA, cRNA and vRNA sequences (An represents a poly(A) tail and GpppNx represents a host capped small RNA with x equal to 10 to 15 nts). (B) the canonical cap-snatching mechanism: IAV RdRP cleaves host capped RNAs at positions 10–15 nts downstream of the 5′ caps and utilizes the last nt (G) of the resulting host capped small RNAs to anneal with the penultimate (-2, C) nt of template vRNAs, initiating mRNA synthesis. (C) Synthesis of IAV cRNA starts with the last nt (-1 U) of template vRNA in a primer-independent manner. (D) Host cap sources of IAV mRNAs. (E) PASR biogenesis: sense PASRs start at the same transcription start sites as the annotated ”gene” and antisense PASRs are mapped ~150 nts upstream of sense PASRs but on the opposite strand. (F) Schemes of chimeric IAV proteins utilizing a start codon ATG in the host capped small RNAs.

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  Figure 2. Noncanonical cap-snatching. (A) In mRNA 3′ clusters, IAV mRNA transcription starts using the basepairing of between the -1 nt (G) of host capped small RNAs and an internal nt C embedded in a 5′CW (W represents A or U) sequence on template vRNAs. (B) In vRNA 5′ regions, IAV RdRP utilizes the -1 nt (G) of host capped small RNAs to anneal with the -2 C of template cRNAs, initiating capped vRNA synthesis.

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  Figure 3. Antiviral RNAi mechanisms. (A) PIR-1 and capping enzyme mediated regulations of ppp-RNAs. (B) Mammallian PIR1 in viral miRNA maturation. Precursor viral miRNAs transcribed by RNA Pol III are cleaved by Dicer to generate duplex siRNAs, which are processed by PIR1 to convert the 5′ triphosphate (blue) to 5′ monophosphate and then loaded to Argonautes (AGO). Without PIR1, only the 3′ part siRNAs (black) are loaded to AGO. (C) 26G-RNA biogenesis: RRF-3 synthesizes short dsRNAs using C nts on template mRNAs, PIR-1/Dicer is recruited to the triphosphorylated dsRNAs, Dicer utilizes a special mode to cleave dsRNAs to generate duplex siRNAs composed of 26G-RNAs and 22mer RNAs with a 3-nt 3′ overhang, PIR-1 removes two phosphates from the triphosphate group on 26G-RNAs, 26G-RNAs are loaded to Argonautes, and the truncated template mRNAs are reused to generate more 26G-RNAs again and again using the same steps as above (the overall process is like a mathematical finite fraction formula). (D) Antiviral RNAi mechanism: the Dicer/DRH-1/PIR-1/RDE-1 complex cleaves dsRNAs to generate duplex 23mer primary siRNAs with a 2-nt 3′ overhang, single stranded primary siRNAs are selectively loaded to…

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  Figure 4. The antivirus sensor piRNA. C. elegans 21U-RNA (21U, piRNA)/Argonaute Piwi related gene 1 (PRG-1) complex binds target RNAs with up to 3 mismatches, RdRP RRF-1 is recruited to generate secondary siRNAs (22Gs) using target RNAs as templates, 22Gs are loaded to WAGOs to form secondary RISCs, and these RISCs directly silence target RNAs.

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  Figure 5. Mammalian antiviral RNAi. Dicer cleaves dsRNAs to generate duplex 22mer siRNAs with a 2-nt 3′ overhang, 22mer siRNAs are loaded to Argonaute AGO2 to form RISCs, and RISCs cleave target RNAs. VSR and IFN signaling suppress Dicer activity; VSR also suppresses RISC activity.