I W Mattaj

..The SMN protein has been found to be part of a multi-component complex that appears to function in the assembly of cellular ribonucleoprotein particles...

..In metazoans, the nuclear envelope breaks down during mitosis and is thought to be completely reabsorbed by the endoplasmic reticulum. How these near neighbours are sorted out at the end of mitosis is an interesting mystery...

..The Ran GTPase is critical in generating this asymmetry. Regulation of nucleocytoplasmic transport generally involves specific inhibition of the formation of a transport complex; however, more global forms of regulation also occur...

..The interaction domain of PHAX with CBC is at least partly distinct from the RNA-binding domain and the NLSs. Thus, the different interaction domains of PHAX allow it to act as a scaffold for the assembly of U snRNA export complexes...

..PHAX phosphorylation is essential for export complex assembly while its dephosphorylation causes export complex disassembly. The compartmentalized PHAX phosphorylation cycle can contribute to the directionality of export...

..These data suggest that the loss of Luc7p disrupts U1 snRNP-CBC interaction, and that this interaction contributes to normal 5' splice site recognition...

..In addition, we identify the Xenopus homologue of the nucleoporin CAN/Nup214 as a RanGTP- and NES cargo-specific binding site for CRM1, suggesting that this nucleoporin plays a role in export complex disassembly and/or CRM1 recycling...

..These results suggest that at least two mechanisms are involved in discrimination of pre-tRNAs and mature tRNAs prior to nuclear export...

..Extracts immunodepleted of CBC do not efficiently splice an adenoviral pre-mRNA owing to blockage of an early step in splicing complex formation. CBC may therefore play a role in pre-mRNA recognition...

..These data indicate that RanBP3 functions by a novel mechanism as a cofactor in recognition and export of certain CRM1 substrates. In vitro, RanBP3 binding to CRM1 affects the relative affinity of CRM1 for different substrates...

..Mutants lacking yCBC were found to be defective in rRNA processing. Analysis of the yCBC deletion phenotype suggests that this is likely to be due to a defect in the splicing of a subset of ribosomal protein mRNA precursors...

..Subsequent NE growth involves a p97-p47 complex. This study provides the first insights into the molecular mechanisms and specificity of fusion events involved in NE formation...

..This activity can be solubilized in the presence of elevated MgCl(2). These data suggest that U1A and U2B" import into the nucleus occurs by a hitherto uncharacterized mechanism...

..Our results therefore reveal functions for Nup153 in NPC assembly, in anchoring NPCs within the NE and in mediating specific nuclear import events...

..Thus, hnRNP F is required for efficient pre-mRNA splicing in vitro and may participate in the effect of CBC on pre-mRNA splicing...

....

..These data suggest that eIF4E binding to the eIF4G-CBC complex on newly exported mRNA displaces CBC, and that the first round of translation on mRNA may occur via a different mechanism than subsequent rounds...

..We also show that inhibition of Ran-GTP production, even in the presence of duplicated centrosomes and kinetochores, prevents assembly of a bipolar spindle in M-phase extracts...

..These results, together with other data, suggest that CBCs play a highly conserved role in the recognition of pre-mRNA substrates at an early step in the splicing process...

..We conclude that CRM1 is an export receptor for leucine-rich nuclear export signals and discuss a model for the role of RanGTP in CRM1 function and in nuclear export in general...

..We propose that RCC1 generates a high local concentration of Ran-GTP around chromatin which in turn induces the local nucleation of microtubules...

..Export complexes form and import complexes disassemble on binding of RanGTP to the receptor. Yeast Los 1 p is a member of the importin-beta family with a poorly defined role in tRNA production...

..Thus, hSRP1 alpha has the properties of a cytosolic receptor for both simple and bipartite NLS motifs...

..Thus, its RNA-binding properties are the sum of those exhibited by human or potato U1A and U2B' proteins. Implications for the role of SNF/D25 in alternative splicing, and for the evolution of the U1A/U2B' protein family, are discussed...

..Fragments of Nup145p and Nup116p including this motif bind specifically to homopolymeric RNAs in vitro. Nup145p, Nup116p, and Nup100p thus represent a novel class of nucleoporins involved in nucleocytoplasmic transport...

..These results demonstrate that CBC mediates the effect of the cap structure in U snRNA export, and provide direct evidence for the involvement of a cellular RNA-binding factor in the transport of RNA to the cytoplasm...

..The promoter region of one of the cloned genes is demonstrated to be functionally active, and to show apparent differences from other pol II promoters...

..These are extremely similar (94.4% identical) between amino acid residues 7 and 114 but much less conserved immediately upstream and downstream from this region...

..Ran functions in these events as a signal for chromosome position...

..In this review we discuss the molecular constituents of the Caenorhabditis elegans NE and describe their role in post-mitotic NE re-formation, as well as the usefulness of C. elegans as an in vivo system for analyzing NE dynamics...

..We propose that the presence of MT binding agents such as NuSAP, which can be directly immobilized on chromatin, are critical for targeting MT production to vertebrate chromosomes during spindle self-organization...

..We propose that phosphorylation of BAF by VRK plays an essential regulatory role in the association of BAF with chromatin and nuclear membrane proteins during NE formation...

..We suggest that interactions of Lem2 with lamins or chromatin are critical for maintaining the integrity of the nuclear envelope...

..We show that MEL-28 is an early-assembling, stable NE component required for all aspects of NE assembly...

..Membrane fractions that are essential for NE formation are shown to bind directly to protein-free DNA, and our data suggest that these interactions are critical for early steps in NE assembly...

..Importantly, NDC1 interacts with Nup53 in vitro. This suggests that NDC1 function involves forming a link between the NE membrane and soluble nucleoporins, thereby anchoring the NPC in the membrane...

..Despite the importance of the NE for eukaryotic cell life, relatively little is known about its biogenesis or many of its functions. We thus are far from understanding the molecular etiology of a diverse group of NE-associated diseases...

..Time-course experiments indicated that Nup155 is recruited to chromatin at the time of NE sealing, suggesting that nuclear pore complex assembly has to progress to a relatively late stage before NE membrane assembly occurs...

....

..Unlike other functions of Importin alpha, this membrane-associated activity does not require interaction with NLS proteins...

..Thus, the contribution to NPC structure of Nup93 and Nup205 is essential for establishment of normal NPC function and for cell viability...

..Depletion also prevented association of FG-repeat nucleoporins with chromatin. We propose a stepwise model in which postmitotic NPC assembly initiates on chromatin via early recruitment of the Nup107-160 complex...

..Finally, we have demonstrated that both IMA-2 and IMB-1, the homologues of vertebrate importin alpha and beta, are essential for both spindle assembly and nuclear formation in early embryos...

..This indicates that chromosome-induced microtubule production is a general requirement for the formation of functional spindles in animal cells...

..Our results indicate that Cdk11 is responsible for RanGTP-dependent MT stabilization around chromosomes and that this local stabilization is essential for normal rates of spindle assembly and spindle function...