Noncoding RNPs of viral origin

Abstract

Like their host cells, many viruses produce noncoding (nc)RNAs. These show diversity with respect to time of expression during viral infection, length and structure, protein-binding partners and relative abundance compared with their host-cell counterparts. Viruses, with their limited genomic capacity, presumably evolve or acquire ncRNAs only if they selectively enhance the viral life cycle or assist the virus in combating the host's response to infection. Despite much effort, identifying the functions of viral ncRNAs has been extremely challenging. Recent technical advances and enhanced understanding of host-cell ncRNAs promise accelerated insights into the RNA warfare mounted by this fascinating class of RNPs.

Figure 1.

(A) VAI and II RNAs. PKR and Dicer interact with nonoverlapping sites on VAI RNA. The apical stem and central domain of VAI RNA bind to and inhibit PKR, respectively, whereas the terminal stems of VAI and VAII RNA interact with Dicer. Cleavage of VAI to produce putative miRNAs has been proposed to leave an upper fragment that remains a potent inhibitor of PKR activity (Wahid et al. 2008). Although there is variation in sequence and length of VA RNAs from different viral strains (RNAs shown are from the much-studied adenovirus type 2 (Ad2)), their general secondary structure is conserved (Ma and Mathews 1996). (B) EBERs1 and 2. EBERs1 and 2 share a high degree of secondary structure and are highly conserved among viruses related to EBV. L22 has been shown to bind to three of EBER1’s stem-loops (Fok et al. 2006a), whereas the La protein binds the polyU tract at the 3′ end of the EBERs (Lerner et al. 1981a). The exact sites of binding of PKR to the EBERs or nucleolin to EBER2 have not been determined.

Figure 2.

(A) HSURs1 and 2. Predicted base-pairing interactions with miR-16, miR-27a and miR-142-3p are shown. Sm binding sites are boxed. Gray and black residues in the HSURs indicate nonconserved and perfectly conserved nucleotides, respectively. Residues in blue indicate perfectly conserved nucleotides involved in interactions with miRNAs. Yellow residues in the miRNAs indicate seed sequences. (B) PAN RNA and the ENE. Putative base-pairing interactions between the internal U-rich loop of the ENE and the poly(A) tail are shown.