Mechanisms and consequences of mRNA destabilization during viral infections

Figures

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  Fig. 1. Herpesviruses host shutoff. A alpha-herpesviruses package the ribonuclease Vhs in their tegument, and it is released into the cytoplasm after viral entry. B Vhs cleaves the host mRNA. The exonuclease Xrn1 further degrades the cleavage fragments. C During late lytic infection, the viral proteins VP16, VP22, and ICP27 bind to and inhibit Vhs from degrading mRNAs. D Gamma-herpesviruses encode the SOX endonuclease, cleaves host mRNAs at an early stage of mRNA translation

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  Fig. 2. IAV Cap-Snatching and PA-X. (1) IAV particles package eight vRNPs that each include a segment of the viral RNA bound to nuceloproteins (NPs) and the viral RdRp. These vRNPs are imported into the nucleus B where they interact with RNA PolII to snatch the caps off of nascent host mRNA transcripts. C The endonuclease PA-X arises from a ribosomal frameshift in the PA gene. D PA-X preferentially cleaves the GCUG motif and the resulting mRNA fragments are further digested by exonucleases

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  Fig. 3. VacV decapping. VacV expresses the proteins D9 and D10 which hydrolyze the m7GTP cap on mRNAs, similar to the host decapping enzyme Dcp2. After decapping, mRNAs are digested by the exonuclease Xrn1

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  Fig. 4. SARS-CoV-2 Nsp1 Host Shutoff. A Schematic of the SARS2 genome and location of Nsp1 gene. B Conservation of Nsp1 amino acid sequence across different βCoVs. Yellow highlight indicates differences compared to SARS2; green highlight is the CTD. C Nsp1 CTD binds the 40S ribosome. Illustrations depict potential Nsp1-40S-mRNA configurations that lead to translation repression and mRNA decay. D SARS2 mRNA encodes a stemloop in its 5ʹ UTR that binds to specific resides on the NTD of Nsp1 and allow the viral mRNA to be translated and escape decay

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  Fig. 5. Consequences of Cytosolic mRNA Decay. Widespread cytosolic mRNA decay causes RPBs to shuttle to the nucleus, where they reduce RNA PolII occupancy and transcription; cause hyper-adenylation of mRNAs (which contributes to nuclear retention); lead to read-through transcription and alternative splicing. All of this leads to an export block of mRNAs, so that mRNAs are trapped in the nucleus