RNA structure interactions and ribonucleoprotein processes of the influenza A virus

Dawson, Wayne K; Lazniewski, Michal; Plewczynski, Dariusz

In the nucleus, the complex of vRNPs separates. The heterotrimer (PA-PB1-PB2) of each vRNP is drawn to the nuclear matrix, where it can bind to RNA polymerase II (Pol II) at the C-terminal domain of the large subunit [73] . By hijacking the host transcriptional machinery, the virus can gain access to many of the host's mRNA processing proteins (the spliceosome complex), the 5 0capped RNA primer sequences, poly(A) tail processing proteins and the host's NEPs; this recruitment process is shown in cartoon style in Figure 1 . The Pol II provides many of the required tools and raw materials needed to build a properly constructed mRNA for export and translation into proteins. One such process is known as cap-snatching [21] , where a short primer sequence at the 5 0 end of the host's mRNA is captured and spliced onto the forming viral mRNA (first two panels of Figure 1 ). Such a primer sequence include the methylated GTP cap (m 7 GDP), a 13 nt primer sequence that permits binding of NEPs and recruits the associated cap-binding proteins (CBPs). By binding Pol II, the transport proteins are snatched before the host CBP can finish processing the host pre-mRNAs [36, 73] . The ability of the vRNA polymerase to inhibit Pol II may slow down or block important host antiviral responses [48, 74] . Other factors involved in packaging the mRNA and constructing the poly(A) tail are also required and provided by Pol II (last two panels of Figure 1 ). M1 and NP also appear to bind to the histones of the nucleosome [36] , which may be necessary to anchor the viral polymerase during replication processes.