Influenza A Segment 7 Splice Site

Influenza A Segment 7 Splice Site
Identifiers
Symbol	IAVS7SS
Other data
RNA type	Cis-reg
Domain(s)	Orthomyxoviridae;
SO	{{{SO}}}

The 3' splice site of the influenza A virus segment 7 pre-mRNA can adopt two different types of RNA structure: a pseudoknot and a hairpin. This conformational switch is proposed to play a role in RNA alternative splicing and may influence the production of M1 and M2 proteins produced by splicing of this pre-mRNA.

This structured region was first discovered in a bioinformatics survey of influenza A based on thermodynamic folding free energy and amino acid codon suppression. Initial models of the secondary structure were based on computational methods for Nucleic acid structure prediction. The hairpin conformation was predicted using RNAalifold, while the pseudoknot was predicted with DotKnot.

Segment 7 encodes the M1 protein and the smaller M2 proton channel protein, which is produced by RNA splicing. M2 protein is critical to the virus: it forms the ion channels that allow for acidification of the virion that stimulates in un-coating. The 3' splice site region used to produce M2 was experimentally probed with structure-sensitive chemicals and enzymes and was found to adopt both the hairpin and pseudoknot conformations in solution. Each conformation places important splicing regulatory sites in different structural environments, which has implications for the modulation of splicing of the segment 7 transcript. For example, the splice site, polypyrimidine tract, branch point, and ASF/SF2 exonic enhancer binding sites are expected to be more accessible in the hairpin conformation and less accessible in the pseudoknot (Figure 1).

By shifting the equilibrium between the pseudoknot and hairpin it may be possible to reduce or enhance M2 splicing, respectively.

This putative mechanism may also be one that is common to spliced influenza transcripts. A similarly placed, but structurally distinct, influenza virus pseudoknot/hairpin was also described in the 3' splice site of segment 8 transcripts, which encode the NP and, by splicing, NEP proteins. These structures form a family of structured RNAs shared between influenza A and influenza B

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