Mechanistic insights into mRNA export through structures of Dbp5.
Nuclear export of mRNA is a critical event in mRNA biogenesis. Passage of mature messenger ribonucleoproteins (mRNPs) through nuclear pore complexes (NPCs) is facilitated by the Mex67/Mtr2 heterodimer. At the NPC cytoplasmic face, the DEAD-box RNA helicase Dbp5 remodels mRNPs by removing Mex67/Mtr2. This remodeling process prevents mRNPs from returning to the nucleus, thereby imposing unidirectionality on mRNA export. Biochemical studies show that Gle1 and inositol hexaphosphate (IP6) activate Dbp5's ATPase activity at the cytoplasmic face of NPC, therefore providing critical spatial regulation of mRNP remodeling during directional transport. Recent structural studies on Dbp5 in free form and in complex with its ligands (ADP, AMPPNP/RNA) as well as with cytoplasmic nucleoporin Nup214 reveal that the binding of ADP or AMPPNP/RNA induces large conformational changes of Dbp5, and RNA and NUP214 bind to Dbp5 in a mutually exclusive manner. These structural data combined with complementary functional analysis significantly advance our understanding on the mechanism governing mRNA export albeit some key issues remain elusive.
Ling
Sharon H M
SH
Laboratory of Macromolecular Structure, Institute of Molecular and Cell Biology, Singapore.
Song
Haiwei
H
D018360:Crystallography, X-Ray; D053487:DEAD-box RNA Helicases / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D029543:Nucleocytoplasmic Transport Proteins / Q000737:chemistry* / Q000378:metabolism*; D034443:RNA Transport; D012333:RNA, Messenger / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry* / Q000378:metabolism*
D029543:Nucleocytoplasmic Transport Proteins; D012333:RNA, Messenger; D029702:Schizosaccharomyces pombe Proteins; C540678:Dbp5 protein, S pombe; C121148:DDX19B protein, human; D053487:DEAD-box RNA Helicases