RNA-regulated interaction of transportin-1 and exportin-5 with the double-stranded RNA-binding domain regulates nucleocytoplasmic shuttling of ADAR1.
Double-stranded RNA (dsRNA)-binding proteins interact with substrate RNAs via dsRNA-binding domains (dsRBDs). Several proteins harboring these domains exhibit nucleocytoplasmic shuttling and possibly remain associated with their substrate RNAs bound in the nucleus during nuclear export. In the human RNA-editing enzyme ADAR1-c, the nuclear localization signal overlaps the third dsRBD, while the corresponding import factor is unknown. The protein also lacks a clear nuclear export signal but shuttles between the nucleus and the cytoplasm. Here we identify transportin-1 as the import receptor for ADAR1. Interestingly, dsRNA binding interferes with transportin-1 binding. At the same time, each of the dsRBDs in ADAR1 interacts with the export factor exportin-5. RNA binding stimulates this interaction but is not a prerequisite. Thus, our data demonstrate a role for some dsRBDs as RNA-sensitive nucleocytoplasmic transport signals. dsRBD3 in ADAR1 can mediate nuclear import, while interaction of all dsRBDs might control nuclear export. This finding may have implications for other proteins containing dsRBDs and suggests a selective nuclear export mechanism for substrates interacting with these proteins.
Fritz
Jutta
J
Department of Chromosome Biology, Max F. Perutz Laboratories, University of Vienna, Vienna, Austria.
Strehblow
Alexander
A
Taschner
Andreas
A
Schopoff
Sandy
S
Pasierbek
Pawel
P
Jantsch
Michael F
MF
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000243:Adenosine Deaminase / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D028884:Karyopherins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D019913:Nuclear Localization Signals / Q000378:metabolism; D012330:RNA, Double-Stranded / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000502:physiology*; D028961:beta Karyopherins / Q000378:metabolism*; D020931:ran GTP-Binding Protein / Q000502:physiology*
D028884:Karyopherins; D019913:Nuclear Localization Signals; D012330:RNA, Double-Stranded; D016601:RNA-Binding Proteins; C108121:TNPO1 protein, human; C446511:XPO5 protein, human; D028961:beta Karyopherins; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase; D020931:ran GTP-Binding Protein