Key result
The influenza A segment 7 mRNA 3' splice site adopts pseudoknot and hairpin conformations, with structural stability varying by host specificity (avian most stable, then swine, then human).
Host-specific RNA stability differences warrant no clinical changes yet; leaves open whether conformations modulate influenza-related cardiac risk.
The 3' splice site of the influenza A segment 7 transcript is utilized to produce mRNA for the critical M2 ion-channel protein. In solution a 63 nt fragment that includes this region can adopt two conformations: a pseudoknot and a hairpin. In each conformation, the splice site, a binding site for the SF2/ASF exonic splicing enhancer and a polypyrimidine tract, each exists in a different structural context. The most dramatic difference occurs for the splice site. In the hairpin the splice site is between two residues that are involved in a 2 by 2 nucleotide internal loop. In the pseudoknot, however, these bases are canonically paired within one of the pseudoknotted helices. The conformational switching observed in this region has implications for the regulation of splicing of the segment 7 mRNA. A measure of stability of the structures also shows interesting trends with respect to host specificity: avian strains tend to be the most stable, followed by swine and then human.
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Moss et al. (2012) studied Influenza A. Influenza A segment 7 mRNA 3' splice site was evaluated on Conformational switching and structural stability. The influenza A segment 7 mRNA 3' splice site adopts pseudoknot and hairpin conformations, with structural stability varying by host specificity (avian most stable, then swine, then human).
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