Directionality of mRNA export Regulated by DEAD-box Helicases
Regulation of directionality of mRNA export is controlled through remodeling of the
mRNPs at the cytoplasmic face of the NPC, where the actions of the essential Dbp5 and Gle1 proteins remodel and release the mRNP into the cytoplasm. Dbp5 is a DEAD-box protein belonging to the RNA helicase superfamily II that binds to the nucleoporin Nup159 on the cytoplasmic filaments of the NPC. Gle1 also binds at the cytoplasmic filaments and, along with its cofactor inositol hexakisphosphate (IP6), specifically stimulates the RNA-dependent ATPase activity of Dbp5. It is the resulting
ADP-bound form of Dbp5 that triggers remodeling of the mRNP. The release of bound ADP from Dbp5 is then stimulated by Nup159. We speculate that this mechanism for regulation of Dpb5 activity may represent a conserved paradigm for the regulation of other DEAD-box helicases. Currently, I am exploring the potential conservation of function and regulation through biochemical characterization of the two human paralogues for Dbp5, DDX19 and DDX25.