How does the viral machinery of transcription cooperate with spliceosome components to regulate viral mRNA splicing ? Which protein-protein and RNA-protein interactions are involved ?
We recently showed that the cellular splicing factors RED and SMU1 are recruited by the viral polymerase and jointly regulate the splicing of the NS1 mRNA into the shorter NS2 mRNA, which encodes a key viral protein named NS2/NEP. In cells depleted for RED or SMU1, the production of infectious influenza virions is strongly reduced, thus indicating that both factors are essential for efficient viral replication (Fournier et al, 2014).
We are now investigating further the biochemical and structural basis of the association between the viral transcriptional machinery and the RED-SMU1 splicing complex, at both the protein and RNA levels. We are also extending our analysis to other components of the splicing machinery that regulate the expression of influenza virus genes.