TRA-1 regulates the cellular distribution of the tra-2 mRNA in C. elegans

Graves, Laura E.; Segal, Scott P.; Goodwin, Elizabeth B.

doi:10.1038/21682

Cited by 38 publications

(19 citation statements)

References 24 publications

(18 reference statements)

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“…There are many other examples of factors and cis-acting sequences that contribute to the regulation of mRNA export. These include the retroviral proteins Rev and Rex, the constitutive transport element of D-type retroviral mRNAs, the Caenorhabditis elegans Zn finger protein TRA-1, the intronless mRNA export elements within the mouse histone H2a mRNA, elements within herpes simplex virus thymidine kinase mRNA and hepatitis B virus RNA, and a retention element within C. elegans splicing factor U2AF mRNA (11,12,14,25,49). In the case of hs mRNA export under stress conditions, however, the evidence in favor of positively acting transport factors and elements is uncertain at best.…”

Section: Discussionmentioning

confidence: 99%

Nuclear Export of Heat Shock and Non-Heat-Shock mRNA Occurs via Similar Pathways

Vainberg

Dower

Rosbash

2000

Molecular and Cellular Biology

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Several studies of the yeast Saccharomyces cerevisiae support differential regulation of heat shock mRNA (hs mRNA) and non-hs mRNA nuclear export during stress. These include the finding that hs mRNA export at 42°C is inhibited in the absence of the nucleoporinlike protein Rip1p (also called Nup42p) (C. A. Saavedra, C. M. Hammell, C. V. Heath, and C. N. Cole, Genes Dev. 11:2845-2856, 1997; F. Stutz, J. Kantor, D. Zhang, T. McCarthy, M. Neville, and M. Rosbash, Genes Dev. 11:2857-2868, 1997). However, the results reported in this paper provide little evidence for selective non-hs mRNA retention or selective hs mRNA export under heat shock conditions. First, we do not detect a block to non-hs mRNA export at 42°C in a wild-type strain. Second, hs mRNA export appears to be mediated by the Ran system and several other factors previously reported to be important for general mRNA export. Third, the export of non-hs mRNA as well as hs mRNA is inhibited in the absence of Rip1p at 42°C. As a corollary, we find no evidence for cis-acting hs mRNA sequences that promote transport during heat shock. Taken together, our data suggest that a shift to 42°C in the absence of Rip1p impacts a late stage of transport affecting most if not all mRNA.In eukaryotic cells, macromolecules are constantly moving between the nucleus and the cytoplasm. Transport occurs through nuclear pore complexes (NPCs), which are imbedded in the double membrane surrounding the nucleus. The NPC is 66 MDa in the yeast Saccharomyces cerevisiae and consists of about 50 different nuclear pore proteins (nucleoporins) (4,34,37,53). Nucleocytoplasmic transport of all macromolecular substrates studied to date is receptor mediated, energy dependent, and saturable (reviewed in references 27 and 33).Accumulating data on protein import and export point to common principles. To access an NPC, transport substrates need to be recognized by soluble receptors. Most well-characterized receptors belong to a family of proteins called ␤-importins or ␤-karyopherins, which recognize specific sequences within their respective substrates. The directionality of transport, nucleus to cytoplasm or cytoplasm to nucleus, is determined in large part by a predicted asymmetry in the intracellular nucleotide-bound status of a key transport player, the small GTPase Ran (Gsp1p in yeast) (17,18,28; reviewed in reference 9). Due to the nuclear localization of the Ran GTP exchange factor (Prp20p in yeast) and the cytoplasmic localization of the Ran GTPase-activating protein (Rna1p in yeast), nuclear Ran is mostly in the GTP-bound form, whereas cytoplasmic Ran is mostly GDP bound. Nuclear Ran-GTP promotes the assembly of several export complexes that are formed by a cooperative association between export cargo, receptor, and Ran-GTP. Ran-GTP hydrolysis in the cytoplasm promotes the dissociation of such export complexes, whereas Ran-GTP in the nucleus promotes the dissociation of import complexes.Upon transcription and processing, mRNA becomes associated with many different RNA-binding proteins, f...

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Section: Discussionmentioning

confidence: 99%

Nuclear Export of Heat Shock and Non-Heat-Shock mRNA Occurs via Similar Pathways

Vainberg

Dower

Rosbash

2000

Molecular and Cellular Biology

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“…Alternatively, mutations that alter the regulation of factors involved in splice site selection may also contribute to tumor formation. In addition, GLI1 has been shown to bind RNA directly at a conserved motif that is distinct from the GLI DNA binding cis-element and to regulate translation of the bound mRNA (37,50). Because these putative GLI binding motifs are present in the pre-mRNA sequence of GLI1, an intriguing possibility is that GLI1 itself or a related protein may determine exon selection.…”

Section: Discussionmentioning

confidence: 99%

“…In this study, we have identified alternative 5Ј UTRs of GLI1 transcripts in mouse and human tissues, which are generated by exon skipping and have marked differences in translation efficiency. Until now, post-transcriptional regulation of GLI1 has been inferred (37), but a precise mechanism has not been determined. Our results suggest that post-transcriptional regulation of GLI1 is mediated by exon skipping and show an association of the most efficiently translated 5Ј UTR transcript with BCC.…”

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confidence: 99%

Post-transcriptional Regulation of the GLI1 Oncogene by the Expression of Alternative 5′ Untranslated Regions

Wang

Rothnagel

2001

Journal of Biological Chemistry

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The oncogene GLI1 is involved in the formation of basal cell carcinoma and other tumor types as a result of the aberrant signaling of the Sonic hedgehog-Patched pathway. In this study, we have identified alternative GLI1 transcripts that differ in their 5 untranslated regions (UTRs) and are generated by exon skipping. These are denoted ␣-UTR, ␤-UTR, and ␥-UTR according to the number of noncoding exons possessed (three, two, and one, respectively). The ␣-and ␤-UTR forms represent the major Gli1 transcripts expressed in mouse tissues, whereas the ␥-UTR is present at relatively low levels but is markedly induced in mouse skin treated with 12-Otetradecanoylphorbol 13-acetate. Transcripts corresponding to the murine ␤ and ␥ forms were identified in human tissues, but significantly, only the ␥-UTR form was present in basal cell carcinomas and in proliferating cultures of a keratinocyte cell line. Flow cytometry analysis determined that the ␥-UTR variant expresses a heterologous reporter gene 14 -23-fold higher than the ␣-UTR and 5-13-fold higher than the ␤-UTR in a variety of cell types. Because expression of the ␥-UTR variant correlates with proliferation, consistent with a role for GLI1 in growth promotion, up-regulation of GLI1 expression through skipping of 5 noncoding exons may be an important tumorigenic mechanism.

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“…7A) demonstrated that these promoter elements were also not necessary for the GLI-2/THP effect to occur. tra-1, the GLI protein of C. elegans, has recently been shown to bind to RNA (32). While in C. elegans this binding affected posttranscriptional events, this observation did suggest that GLI-2/THP might interact with RNA elements within the HIV promoters.…”

Section: Gli-2/thp Decreases Expression From the Htlv-1 But Not Htlv-mentioning

confidence: 66%

GLI-2 Modulates Retroviral Gene Expression

Smith¹,

Gitlin²,

Browning

et al. 2001

J Virol

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GLI proteins are involved in the development of mice, humans, zebrafish, Caenorhabditis elegans, Xenopus, and Drosophila. While these zinc finger-containing proteins bind to TG-rich promoter elements and are known to regulate gene expression in C. elegans and Drosophila, mechanistic understanding of how regulation is mediated through naturally occurring transcriptional promoters is lacking. One isoform of human GLI-2 appears to be identical to a factor previously called Tax helper protein (THP), thus named due to its ability to interact with a TG-rich element in the human T-lymphotropic virus type 1 (HTLV-1) enhancer thought to mediate transcriptional stimulation by the Tax protein of HTLV-1. We now demonstrate that, working through its TG-rich binding site and adjacent elements, GLI-2/THP actually suppresses gene expression driven by the HTLV-1 promoter. GLI-2/THP has no effect on the HTLV-2 promoter, activates expression from the promoters of human immunodeficiency virus types 1 and (HIV-1 and -2), and stimulates HIV-1 replication. Both effective suppression and activation of gene expression and viral replication require the first of the five zinc fingers, which is not necessary for DNA binding, to be intact. Thus, not only can GLI-2/THP either activate or suppress gene expression, depending on the promoter, but the same domain (first zinc finger) mediates both effects. These findings suggest a role for GLI-2 in retroviral gene regulation and shed further light on the mechanisms by which GLI proteins regulate naturally occurring promoters.

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TRA-1 regulates the cellular distribution of the tra-2 mRNA in C. elegans

Cited by 38 publications

References 24 publications

Nuclear Export of Heat Shock and Non-Heat-Shock mRNA Occurs via Similar Pathways

Nuclear Export of Heat Shock and Non-Heat-Shock mRNA Occurs via Similar Pathways

Post-transcriptional Regulation of the GLI1 Oncogene by the Expression of Alternative 5′ Untranslated Regions

GLI-2 Modulates Retroviral Gene Expression

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