Nuclear export factor RBM15 facilitates the access of DBP5 to mRNA.
The conserved mRNA export receptor NXF1 (Mex67 in yeast) assembles with messenger ribonucleoproteins (mRNP) in the nucleus and guides them through the nuclear pore complex into the cytoplasm. The DEAD family RNA helicase Dbp5 is essential for nuclear export of mRNA and is thought to dissociate Mex67 from mRNP upon translocation, thereby generating directional passage. However, the molecular mechanism by which Dbp5 recognizes Mex67-containing mRNP is not clear. Here we report that the human NXF1-binding protein RBM15 binds specifically to human DBP5 and facilitates its direct contact with mRNA in vivo. We found that RBM15 is targeted to the nuclear envelope, where it colocalizes extensively with DBP5 and NXF1. Gene silencing of RBM15 leads to cytoplasmic depletion and nuclear accumulation of general mRNA as well as individual endogenous transcripts, indicating that RBM15 is required for efficient mRNA export. We propose a model in which RBM15 acts locally at the nuclear pore complex, by facilitating the recognition of NXF1-mRNP complexes by DBP5 during translocation, thereby contributing to efficient mRNA export.
Human Retrovirus Pathogenesis Section, National Cancer Institute-Frederick, Frederick, MD 21702-1201, USA.
Andrei S
AS
Zolotukhin
Hiroaki
H
Uranishi
Susan
S
Lindtner
Jenifer
J
Bear
George N
GN
Pavlakis
Barbara K
BK
Felber
D002460:Cell Line; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D006801:Humans; D009685:Nuclear Envelope / Q000378:metabolism; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism*; D034622:RNA Interference; D012326:RNA Splicing; D034443:RNA Transport; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism
D029543:Nucleocytoplasmic Transport Proteins; C431574:RBM15 protein, human; C546581:RBM15B protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; C026452:messenger ribonucleoprotein; C121148:DDX19B protein, human; D053487:DEAD-box RNA Helicases