Nuclear export factor family protein participates in cytoplasmic mRNA trafficking.
In eukaryotes, the nuclear export of mRNA is mediated by nuclear export factor 1 (NXF1) receptors. Metazoans encode additional NXF1-related proteins of unknown function, which share homology and domain organization with NXF1. Some mammalian NXF1-related genes are expressed preferentially in the brain and are thought to participate in neuronal mRNA metabolism. To address the roles of NXF1-related factors, we studied the two mouse NXF1 homologues, mNXF2 and mNXF7. In neuronal cells, mNXF2, but not mNXF7, exhibited mRNA export activity similar to that of Tip-associated protein/NXF1. Surprisingly, mNXF7 incorporated into mobile particles in the neurites that contained poly(A) and ribosomal RNA and colocalized with Staufen1-containing transport granules, indicating a role in neuronal mRNA trafficking. Yeast two-hybrid interaction, coimmunoprecipitation, and in vitro binding studies showed that NXF proteins bound to brain-specific microtubule-associated proteins (MAP) such as MAP1B and the WD repeat protein Unrip. Both in vitro and in vivo, MAP1B also bound to NXF export cofactor U2AF as well as to Staufen1 and Unrip. These findings revealed a network of interactions likely coupling the export and cytoplasmic trafficking of mRNA. We propose a model in which MAP1B tethers the NXF-associated mRNA to microtubules and facilitates their translocation along dendrites while Unrip provides a scaffold for the assembly of these transport intermediates.
Tretyakova
Irina
I
Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, NCI-Frederick, National Institutes of Health, Frederick, Maryland 21702, USA.
Zolotukhin
Andrei S
AS
Tan
Wei
W
Bear
Jenifer
J
Propst
Friedrich
F
Ruthel
Gordon
G
Felber
Barbara K
BK
D021581:Active Transport, Cell Nucleus / Q000235:genetics; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism*; D017930:Genes, Reporter; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D029543:Nucleocytoplasmic Transport Proteins / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism*; D012335:RNA, Ribosomal / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism; D014407:Tumor Cells, Cultured; D020798:Two-Hybrid System Techniques
D002352:Carrier Proteins; D008074:Lipoproteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D029543:Nucleocytoplasmic Transport Proteins; C502321:Nxf2 protein, mouse; C502322:Nxf7 protein, mouse; D012333:RNA, Messenger; D012335:RNA, Ribosomal; D016601:RNA-Binding Proteins; C403447:STRAP protein, human; C492187:Stau1 protein, mouse; D015534:Trans-Activators; C500212:tocopherol-associated protein, mouse