Nuclear Export Factor Family Protein Participates in Cytoplasmic mRNA Trafficking

Abstract

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 Tipassociated 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 brainspecific 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.

Detection of genomic copy number changes in patients with idiopathic mental retardation by high-resolution X-array-CGH: important role for increased gene dosage ofXLMRgenes

“…Nevertheless, a preferential inactivation (480%) of one of the X-chromosomes was found in the mothers of Cases 1, 7, and 8 (Table 1; column ''Xinactivation'') and provides additional evidence for causality, which was confirmed for the MECP2 duplication in Case 7 [Van Esch et al, 2005a]. Case 8 harbors a 0.8-Mb duplication at Xp22 including the candidate MR gene NXF5 implicated in mRNA transport in dendrites [Jun et al, 2001], and later confirmed for the mouse homolog Nxf7 [Tretyakova et al, 2005]. Therefore, increased dosage of NXF5 might disturb storage levels of particular mRNAs in neurons.…”

Dm nxf1/sbr gene affects the formation of meiotic spindle in female Drosophila melanogaster

“…It is known that NXF1 proteins function as a part of macromolecular complexes and interact with different factors (Kataoka et al 2000;Stutz et al 2000;Le Hir et al 2001;Rodrigues et al 2001;Gatfield and Izaurralde 2002;Blevins et al 2003;Huang et al 2003;Forler et al 2004;Ooe et al 2004;Tretyakova et al 2005). Such interactions have been demonstrated for orthologues of Dm NXF1 in humans (Hs NXF1/TAP) and mice (Mm NXF1).…”

“…The genes of this family are involved in controlling the transport of mRNA Herold et al 2001;Jun et al 2001;Sasaki et al 2005;Tretyakova et al 2005). The sbr or Dm nxf1 gene of Drosophila melanogaster encodes the main transport receptor of mRNA and is orthologous to the Tap/Hs nxf1 gene of humans and the Mm nxf1 gene of mice (Herold et al , 2003Sasaki et al 2005;Tretyakova et al 2001).…”

“…Both sequences of the C-terminus part of the protein are important for transporting the complex through the NPC (Braun et al , 2002Fribourg et al 2001). Functioning in macromolecular complexes, they interact with various partner proteins, including those that are involved in forming the cell division apparatus (Blevins et al 2003;Tretyakova et al 2005). It is, thus, important to determine the domains of SBR protein that lead to chromosome instability.…”

Light Chain 1 of Microtubule-associated Protein 1B Can Negatively Regulate the Action of Pes1

“…Although most studies of Mtap1b-LC1 have centered on its interaction with microtubules, several roles have been proposed for microtubule-associated proteins in processes that may be independent of microtubule function. For example, in neuroblastoma cells Tau-1 has been identified in the fibrillar component of nucleoli as well as in the nucleolar organizer regions, both places where ribosome biogenesis is initiated (40), and Mtap1b-LC1 has been shown to interact with proteins involved in diverse processes such as mRNA trafficking and cAMP signaling (47,48). It is, therefore, plausible that the inter-action of Pes1 with Mtap1b-LC1 is unrelated to the binding of Mtabp1b-LC1 to microtubules and could reflect an as-yet unidentified role for Mtap1b-LC1 in controlling ribosome formation.…”