Fig. 4. Functional implications of the FluPol_C-ANP32A complex.

a, Relative positions of the RNA product exit channel in FluPol^R and the 5’ RNA binding site in FluPol^E in the chANP32A-FluPol_C complex. The positions of the RNA product exit channel in FluPol^R and the 5’ RNA binding site in FluPol^E were determined by superposing FluPol^R and FluPol^E with the structure of FluPol_A bound to capped RNA and vRNA template (PDB 6RR7). b, Model for the role of FluPol-ANP32A complex in the replication of the influenza virus RNA genome and its assembly into RNP. FluPol in the context of vRNP or cRNP is flexible (1) but is stabilised in a replicase FluPol^R conformation upon binding of a newly synthesised FluPol in the presence of ANP32A (2). FluPol^R initiates replication in a primer independent manner (3) with a trans-activating FluPol involved in cRNA to vRNA replication by promoting cRNA template realignment (3’). As the 5’ end of the nascent replication product is released from the polymerisation active site of FluPol^R, it is captured in the 5’ RNA binding pocket of the encapsidating FluPol^E bound to FluPol^R (4), initiating the encapsidation of the nascent RNA with NP (5). Nascent vRNA or cRNA assemble into vRNP or cRNP, respectively (6), and are released upon FluPol^R termination. FluPol^E becomes the resident polymerase of the newly produced vRNP or cRNP.