NXF-2, REF-1, and REF-2 Affect the Choice of Nuclear Export Pathway for tra-2 mRNA in C. elegans

Kuersten, Scott; Segal, Scott P.; Verheyden, Jamie M.; LaMartina, Sarah M; Goodwin, Elizabeth B.

doi:10.1016/j.molcel.2004.05.004

Cited by 47 publications

(49 citation statements)

References 35 publications

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“…The adaptor for the 40S ribosomal subunit is not yet known, although Yrb2 is a candidate for this role (36). Adaptor proteins that have been proposed to mediate export of some specific mRNAs via the Crm1 pathway include the HuR-pp32-APRIL complex (2), the human nuclear export family member NXF3 (60), a splice variant of Staufen2 (33), and possibly TRA-1 in Caenorhabditis elegans, although this association has yet to be confirmed (27).…”

Section: Discussionmentioning

confidence: 99%

Detailed Mapping of the Nuclear Export Signal in the Rous Sarcoma Virus Gag Protein

Scheifele¹,

Ryan²,

Parent

2005

J Virol

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). In addition, export of Gag from the nucleus was found to be a rate-limiting step in virus-like particle production. Consistent with a role for the NES sequence in viral replication, this cluster of hydrophobic residues in p10 is conserved across a wide range of avian retroviruses. Furthermore, naturally occurring substitutions within this region in related viruses maintained nuclear export activity and remained sensitive to the activity of LMB. Using gain-of-function approaches, we found that the hydrophobic motif in p10 was sufficient to promote the nuclear export of a heterologous protein and was positionally independent within the Gag polyprotein. Finally, the export pathway was further defined by the ability of specific nucleoporin inhibitors to prevent the egress of Gag from the nucleus, thereby identifying additional cellular mediators of RSV replication.The Gag polyprotein coordinates the assembly of retroviral particles by serving as the precursor to the structural components of the virion, by selecting the RNA genome for encapsidation into the assembling particle, and, for some retroviruses, by directing the incorporation of the envelope glycoproteins. Gag proteins of Rous sarcoma virus (RSV) are initially synthesized on cytosolic ribosomes and then traffic through the cell nucleus (49). Within the cytoplasm, retroviral assembly intermediates can be isolated that are comprised of Gag protein multimers upon an RNA scaffold (31,37,50,55). These Gag-RNA complexes are then targeted specifically to the plasma membrane, which serves as the site for higher-order virus assembly. Approximately 1,500 Gag proteins associate at the plasma membrane, where they can be seen as electrondense aggregates driving the formation of a spherical bud. Following release, the immature virion is processed by the viral protease, cleaving the RSV Gag protein into the structural proteins matrix (MA), capsid, and nucleocapsid (NC), the enzyme protease (PR), and the peptides p2a, p2b, p10, and SP.Coordination of retroviral assembly is directed by three functional domains within the Gag polyprotein: the membrane-binding domain mediates the selective targeting to and stable binding of the plasma membrane, the interaction domains facilitate multimerization of Gag proteins and RNA binding, and the late domain recruits host cell machinery to separate the emerging virion from the membrane (44). However, the precise compartment within the cell where each step of the assembly process occurs remains unclear. Moreover, the specific subcellular targeting signals within Gag have been only partially defined. For example, although several nuclear localization signals (NLSs) have been identified within Gag polyproteins, their roles in retroviral replication are uncertain. NLSs have been identified in the Gag proteins of the Schizosaccharomyces pombe Tf1 element (10) and the HeT-A and TART retrotransposons of Drosophila (48). Certain Gag proteins localize partially to the nucleus under steady-state conditions, including the Gag proteins of the hum...

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Section: Discussionmentioning

confidence: 99%

Detailed Mapping of the Nuclear Export Signal in the Rous Sarcoma Virus Gag Protein

Scheifele¹,

Ryan²,

Parent

2005

J Virol

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“…TRA-1 binds to and stimulates export of the tra-2 mRNA in a manner that is sensitive to the XPO-1 inhibitor leptomycin B: nuclear levels of TRA-1 increase in males treated with leptomycin B and production of yolk proteins and oocytes is induced (Segal et al 2001). Nuclear export of TRA-1 protein and tra-2 mRNA also depends on the factors NXF-2, ALY-1, and ALY-2 (Kuersten et al 2004), which all seem dispensable for bulk mRNA export (MacMorris et al 2003).…”

Section: Nuclear Localization and Nuclear Export Signalsmentioning

confidence: 99%

Cell Biology of theCaenorhabditis elegansNucleus

Cohen-Fix

Askjaer

2017

Genetics

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Studies on the Caenorhabditis elegans nucleus have provided fascinating insight to the organization and activities of eukaryotic cells. Being the organelle that holds the genetic blueprint of the cell, the nucleus is critical for basically every aspect of cell biology. The stereotypical development of C. elegans from a one cell-stage embryo to a fertile hermaphrodite with 959 somatic nuclei has allowed the identification of mutants with specific alterations in gene expression programs, nuclear morphology, or nuclear positioning. Moreover, the early C. elegans embryo is an excellent model to dissect the mitotic processes of nuclear disassembly and reformation with high spatiotemporal resolution. We review here several features of the C. elegans nucleus, including its composition, structure, and dynamics. We also discuss the spatial organization of chromatin and regulation of gene expression and how this depends on tight control of nucleocytoplasmic transport. Finally, the extensive connections of the nucleus with the cytoskeleton and their implications during development are described. Most processes of the C. elegans nucleus are evolutionarily conserved, highlighting the relevance of this powerful and versatile model organism to human biology.KEYWORDS Caenorhabditis elegans; chromatin; gene expression; lamin; LEM-domain proteins; LINC; P granule; nuclear pore complex; nuclear envelope; nucleocytoplasmic transport; nucleolus; WormBook TABLE OF CONTENTSAbstract 25 C. elegans as a model system to study cell biology of the nucleus 26 Structural components of the nucleus 27

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“…The export of TRA-1 protein and tra-2 mRNA is interdependent and a deletion of the TRA-1-binding element in tra-2 mRNA results in the nuclear accumulation of both TRA-1 protein and tra-2 mRNA (Segal et al 2001 ) . Importantly, tra-2 mRNA is not exported via the canonical RNA export pathway of polyadenylated mRNAs, but rather uses an alternative pathway mediated by NXF-2, REF-1, and REF-2, which facilitates a more ef fi cient translation regulation (Kuersten et al 2004 ) . Other conserved general RNA regulators, such as members of the exon junction complex affect the sperm-to-oocyte switch and likely regulate components of the sex determination pathway (Li et al 2000 ) .…”

Section: Multidimensional Translational Control Of Tra-2 Mrnamentioning

confidence: 99%

Translational Control in the Caenorhabditis elegans Germ Line

Nousch

Eckmann

2012

Advances in Experimental Medicine and Biology

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Translational control is a prevalent form of gene expression regulation in the Caenorhabditis elegans germ line. Linking the amount of protein synthesis to mRNA quantity and translational accessibility in the cell cytoplasm provides unique advantages over DNA-based controls for developing germ cells. This mode of gene expression is especially exploited in germ cell fate decisions and during oogenesis, when the developing oocytes stockpile hundreds of different mRNAs required for early embryogenesis. Consequently, a dense web of RNA regulators, consisting of diverse RNA-binding proteins and RNA-modifying enzymes, control the translatability of entire mRNA expression programs. These RNA regulatory networks are tightly coupled to germ cell developmental progression and are themselves under translational control. The underlying molecular mechanisms and RNA codes embedded in the mRNA molecules are beginning to be understood. Hence, the C. elegans germ line offers fertile grounds for discovering post-transcriptional mRNA regulatory mechanisms and emerges as great model for a systems level understanding of translational control during development.

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NXF-2, REF-1, and REF-2 Affect the Choice of Nuclear Export Pathway for tra-2 mRNA in C. elegans

Cited by 47 publications

References 35 publications

Detailed Mapping of the Nuclear Export Signal in the Rous Sarcoma Virus Gag Protein

Detailed Mapping of the Nuclear Export Signal in the Rous Sarcoma Virus Gag Protein

Cell Biology of theCaenorhabditis elegansNucleus

Translational Control in the Caenorhabditis elegans Germ Line

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