The Battle for Survival: The Role of RNA Non-Canonical Tails in the Virus–Host Interaction

Figures

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  Figure 1. The proposed model for the action mechanism of mixed tailing. (A,B) TENT4A/4B stabilizes mRNA by generating mixed A/G tailing in human cells. PAN2/3 shortens poly(A) tail to 110 nt, and CCR4-NOT removes the remaining A-residues. TENT4A/4B decorates poly(A) tail with guanosine residues. Compared with pure poly(A) tail, mixed A/G tail is more resistant to CCR4-NOT-complex-mediated deadenylation since CCR4-NOT sheds once it encounters G-residue. After deadenylation and decapping, all mRNAs are degraded from both 5′ and 3′ ends. (C) Mixed A/G tails regulate translation efficiency in Arabidopsis. Guanosines are supposed to divide the poly(A) tail into interspersed A-segments, thereby reducing binding efficiency between PABP and A-tail and translation efficiency of Arabidopsis mRNA.

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  Figure 2. The proposed models for virus RNA stabilization by ZCCHC14-TENT4A/4B complex. (A) A model for inhibition of HCMV RNA2.7 and HBV mRNA stability by RG7834. TENT4A/4B is recruited by ZCCHC14 to the stem-loop of PRE in viral mRNA 3′ UTR, and thereby generating 3′ mixed tails at viral mRNA and disturbing CCR4-NOT-mediated RNA decay. RG7834 inhibits terminal nucleotidyltransferase activity of TENT4, destabilizing HBV and HCMV transcripts. (B) A model for RG7834 inhibition of HAV RNA synthesis. ZCCHC14 binds to stem-loop Vb in the HAV 5′ UTR and TENT4 might recognize the 3′ end of polyadenylated HAV genome RNA. ZCCHC14 and TENT4 interaction serves as a bridge that facilitates functional cyclization of the genome toward synthesizing its complementary RNA. RG7834 disrupts interaction between TENT4A/4B with ZCCHC14, interrupting genome cyclization and impeding genome RNA replication.

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  Figure 3. Overview of antiviral innate immune pathways. Interferon pathway (left), RNAi pathway (middle), terminal uridylation (right) resist virus infection. Viral RNA is uridylated by terminal uridylyltransferase CDE-1 in C. elegans and TUT4/7 in mammals. The U-tagged RNA undergoes a degradation pathway.