Dawson, A.R., Wilson, G.M., Freiberger, E.C., Mondal, A., Coon, J.J., and Mehle, A. (2020). Phosphorylation controls RNA binding and transcription by the influenza virus polymerase. PLOS Pathog. 16, e1008841.
The influenza virus polymerase is a multifunctional enzyme directing viral gene expression and genome replication. Immediately following infection, the polymerase primarily performs transcription to make the viral mRNAs that program the replication cycle. The polymerase then shifts output to produce more copies of the viral genome at later stages of infection. The balance between transcription and replication is critical for successful infection. Here we identify phosphorylation sites within the viral polymerase and describe how these post-translational modifications control polymerase activity. Cellular kinases modify the viral polymerase. We identified a phosphorylation site in the catalytic subunit PB1 that selectively disables transcription, but not replication. We also describe a phosphorylation site in PB1 that disrupts binding to viral RNAs, disabling all activities of the polymerase. These modifications may establish polymerases with specialized function, and help regulate the balance between transcription and replication throughout the viral life cycle.