Proposed model for non-canonical cytoplasmic processing of virus-encoded miRNA-like structures in a Drosha-dependent manner. The PI3K/Akt pathway is known to be activated early during flavivirus infection, which in turn leads to the GSK3β inactivation by phosphorylation at Serine9. GSK3β is the kinase responsible of Drosha phosphorylation at residues Serine300 or Serine302, which is required for its nuclear localization. In the absence of active GSK3β, the unphosphorylated Drosha should accumulate in the cytoplasm where it should be available to start a non-canonical cytoplasmic miRNA biogenesis pathway. To establish if the absence of Drosha phosphorylation is enough for explaining its resulting cytoplasmic pattern, or the nuclear Drosha is actively relocalized to the cytoplasm remains to be demonstrated.
Usme-Ciro et al. Virology Journal 2013 10:185 doi:10.1186/1743-422X-10-185