Shu Zhou, Rute Maria Pinto, Hou Wei Chook, Eleanor. [preprint]Identification of cis-Acting Elements that Regulate Influenza A Virus Segment 7 Differential mRNA Splicing. https://doi.org/10.64898/2025.12.22.695654
Influenza A virus segment 7 encodes the M1 matrix protein and M2 ion channel from an unspliced primary transcript mRNA1 and spliced mRNA2, respectively. Both proteins are essential for efficient virus replication, but the intrinsic sequences that determine segment 7 splicing balance are not fully defined. Here, we systematically investigated how conserved cis-acting splicing elements regulate 7 splicing. We found that while the splice acceptor sequence is optimal, both potential upstream polypyrimidine tracts regulate splicing, the 5´ region acting positively and the 3´ region negatively to maintain M1 expression. We could not unambiguously identify the mRNA2 branch point, but two closely spaced motifs can act redundantly. Saturation mutagenesis of the mRNA2 splice donor sequence showed that it is nearly optimal but that nucleotides 51 and 55 modestly downregulate splicing efficiency. Most introduced mutations that change splicing balance are nonsynonymous in M1. Nevertheless, mutations in the polypyrimidine tract and branch points that significantly perturbed M1:M2 balance resulted in viable viruses. In contrast, the splice donor sequence was intolerant of mutation. We conclude that M1:M2 balance is maintained via suboptimal splice donor and polypyrimidine tract splicing signals, with the latter allowing more evolutionary flexibility to vary the ratio and/or M1 sequence.
See Also:
Latest articles in those days:
- Host Species Contribution to the Spatiotemporal Dynamics of the 2024-2025 H5N1 Epidemic in Italy 16 hours ago
- mRNA-based influenza vaccine expands the B cell response breadth in humans 16 hours ago
- Molecular surveillance and predictive risk modelling of avian influenza virus in wild birds in Egypt 16 hours ago
- Germany as a key transit hub for the emergence and spread of high pathogenicity avian influenza H5 clade 2.3.4.4b reassortants in Europe 2 days ago
- Degradation of ACSL3 by influenza A virus shifts unfolded protein response from antiviral defense to viral evasion 2 days ago
[Go Top] [Close Window]


