Translational regulation of tra-2 by its 3′ untranslated region controls sexual identity in C. elegans

Goodwin, Elizabeth B.; Okkema, Peter G.; Evans, Thomas C.; Kimble, Judith

doi:10.1016/0092-8674(93)80074-o

Cited by 187 publications

(155 citation statements)

References 42 publications

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“…In addition, the bulk of the GLUT1 mRNA was associated with heavier (more dense) polysomes, consistent with an increased efficiency of ribosome loading and translation of this message. This interpretation is supported by studies on the translational regulation of tra-2, in which deletion of a negative control region from the 3ЈUTR led to an increased rate of translation coincident with movement of the message to the heavy (more dense) polysomes (17). This effect on the initiation of protein synthesis may result in both the stabilization of the GLUT1 mRNA and the increased synthesis of GLUT1 protein.…”

Section: Fig 7 Membrane Distribution Of Glut1 Protein In Untransfecsupporting

confidence: 60%

Ectopic Expression of Hel-N1, an RNA-Binding Protein, Increases Glucose Transporter (GLUT1) Expression in 3T3-L1 Adipocytes

Jain

Andrews

McGowan

et al. 1997

Molecular and Cellular Biology

187

174

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3T3-L1 preadipocytes ectopically expressing the mammalian RNA-binding protein Hel-N1 expressed up to 10-fold more glucose transporter (GLUT1) protein and exhibited elevated rates of basal glucose uptake. Hel-N1 is a member of the ELAV-like family of proteins associated with the induction and maintenance of differentiation in various species. ELAV proteins are known to bind in vitro to short stretches of uridylates in the 3 untranslated regions (3 UTRs) of unstable mRNAs encoding growth-regulatory proteins involved in transcription and signal transduction. GLUT1 mRNA also contains a large 3 UTR with a U-rich region that binds specifically to Hel-N1 in vitro. Analysis of the altered GLUT1 expression at the translational and posttranscriptional levels suggested a mechanism involving both mRNA stabilization and accelerated formation of translation initiation complexes. These findings are consistent with the hypothesis that the Hel-N1 family of proteins modulate gene expression at the level of mRNA in the cytoplasm.Interaction of RNA-binding proteins with cis elements in mRNAs is believed to be involved in regulation of their stability and translational efficiency (reviewed in reference 32). The regulated stability of transferrin, granulocyte-macrophage colony-stimulating factor, and histone mRNAs has been shown, at least in part, to be controlled by the binding of specific proteins to consensus sequences in the 3Ј untranslated region (3ЈUTR) of these messages (3, 37, 41). Studies of tobacco mosaic virus, the Drosophila melanogaster developmental gene hunchback, human cytokine, and 15-lipoxygenase mRNAs have demonstrated that the 3ЈUTR also contains information capable of regulating translational efficiency which may be mediated by RNA-binding proteins (13,25,35,36). A major class of RNA-binding proteins which possess an 80-amino-acid consensus element, termed the RNA recognition motif (RRM) (39), which forms the core of a functional RNAbinding domain has been identified.Hel-N1 (human embryonic lethal abnormal vision [ELAV]-like neuronal protein 1), a mammalian homolog of Drosophila ELAV, is an mRNA-binding protein of the RRM family (15,16,27). Recent studies on Hel-N1, and the alternative form, Hel-N2 (lacking a 13-amino-acid segment between RRM2 and RRM3), in human medulloblastoma cells and embryonic carcinoma P19 cells have indicated that it plays a role in mRNA metabolism (15). These proteins are bound to poly(A) ϩ mRNA in granular RNP structures, and their expression is upregulated during neuronal cell differentiation of P19 cells (15). Likewise, hNT2 cells when induced to differentiate by retinoic acid exhibited a marked increase in the expression of human ELAV-like proteins which colocalized with mRNPs associated with polysomes (1). Hence, data from both of these studies support an important role for mammalian ELAV-like proteins in the processes of cell growth and differentiation.Interestingly, members of the ELAV family have been shown to bind the AU-rich regions of the 3ЈUTRs in cytokine and proto-oncogene m...

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Section: Fig 7 Membrane Distribution Of Glut1 Protein In Untransfecsupporting

confidence: 60%

Ectopic Expression of Hel-N1, an RNA-Binding Protein, Increases Glucose Transporter (GLUT1) Expression in 3T3-L1 Adipocytes

Jain

Andrews

McGowan

et al. 1997

Molecular and Cellular Biology

187

174

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“…GLD-1 binds a short motif in its mRNA targets, the STAR protein-binding element (SBE) (33) or GLD-1-binding motif (GBM) (38). In Ce-tra-2, GLD-1 binding sites are found within larger direct repeat elements (DREs) (28), containing three SBEs/GBMs, plus a fourth candidate site more 5′ in the 3′ UTR (Fig. 5B).…”

Section: Resultsmentioning

confidence: 99%

“…Germ-line hyperactivity of tra-2 is a cause of germ-line feminization in XX Ce-gld-1 mutants (22,28). C. briggsae tra-2 plays a conserved female-promoting role in both the soma and germ line (34,47).…”

Section: Resultsmentioning

confidence: 99%

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Independent recruitments of a translational regulator in the evolution of self-fertile nematodes

Beadell

Liu²,

Johnson³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Pleiotropic developmental regulators have been repeatedly linked to the evolution of anatomical novelties. Known mechanisms include cis-regulatory DNA changes that alter regulator transcription patterns or modify target-gene linkages. Here, we examine the role of another form of regulation, translational control, in the repeated evolution of self-fertile hermaphroditism in Caenorhabditis nematodes. Caenorhabditis elegans hermaphrodites initiate spermatogenesis in an otherwise female body through translational repression of the gene tra-2. This repression is mediated by GLD-1, an RNA-binding protein also required for oocyte meiosis and differentiation. By contrast, we show that in the convergently hermaphroditic Caenorhabditis briggsae, GLD-1 acts to promote oogenesis. The opposite functions of gld-1 in these species are not gene-intrinsic, but instead result from the unique contexts for its action that evolved in each. In C. elegans, GLD-1 became essential for promoting XX spermatogenesis via changes in the tra-2 mRNA and evolution of the species-specific protein FOG-2. C. briggsae GLD-1 became an essential repressor of sperm-promoting genes, including Cbr-puf-8, and did not evolve a strong association with tra-2. Despite its variable roles in sex determination, the function of gld-1 in female meiotic progression is ancient and conserved. This conserved role may explain why gld-1 is repeatedly recruited to regulate hermaphroditism. We conclude that, as with transcription factors, spatially localized translational regulators play important roles in the evolution of anatomical novelties.germ cells | translation | breeding systems | mutant

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“…Third, the sexual fate of the germ line is governed by a balance between the activities of tra-2 and fem-3 (Barton et al 1987;Schedl and Kimble 1988). Both tra-2 and fem-3 are subject to post-transcriptional repression, mediated by their 3Ј untranslated regions (3Ј UTR), in the germ line (Doniach 1986;Barton et al 1987;Ahringer and Kimble 1991;Goodwin et al 1993). We suggest that the protein-protein interaction between TRA-2A (or TRA-2B) and FEM-3 that we have described provides a second level of control over fem-3 activity in the XX germ line.…”

Section: Significance Of Tra-2/fem-3 Interaction For Germ-line Sex Dementioning

confidence: 99%

Negative regulation of male development in Caenorhabditis elegans by a protein-protein interaction between TRA-2A and FEM-3

Mehra¹,

Gaudet²,

Heck³

et al. 1999

Genes & Development

103

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The tra-2 gene of the nematode Caenorhabditis elegans encodes a predicted membrane protein, TRA-2A, that promotes XX hermaphrodite development. Genetic analysis suggests that tra-2 is a negative regulator of three genes that are required for male development: fem-1, fem-2, and fem-3. We report that the carboxy-terminal region of TRA-2A interacts specifically with FEM-3 in the yeast two-hybrid system and in vitro. Consistent with the idea that FEM-3 is a target of negative regulation, we find that excess FEM-3 can overcome the feminizing effect of tra-2 and cause widespread masculinization of XX somatic tissues. In turn, we show that the masculinizing effects of excess FEM-3 can be suppressed by overproduction of the carboxy-terminal domain of TRA-2A. A FEM-3 fragment that retains TRA-2A-binding activity can masculinize fem-3(+) animals, but not fem-3 mutants, suggesting that it is possible to release and to activate endogenous FEM-3 by titrating TRA-2A. We propose that TRA-2A prevents male development by interacting directly with FEM-3 and that a balance between the opposing activities of TRA-2A and FEM-3 determines sex-specific cell fates in somatic tissues. When the balance favors FEM-3, it acts through or with the other FEM proteins to promote male cell fates.

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Translational regulation of tra-2 by its 3′ untranslated region controls sexual identity in C. elegans

Cited by 187 publications

References 42 publications

Ectopic Expression of Hel-N1, an RNA-Binding Protein, Increases Glucose Transporter (GLUT1) Expression in 3T3-L1 Adipocytes

Ectopic Expression of Hel-N1, an RNA-Binding Protein, Increases Glucose Transporter (GLUT1) Expression in 3T3-L1 Adipocytes

Independent recruitments of a translational regulator in the evolution of self-fertile nematodes

Negative regulation of male development in Caenorhabditis elegans by a protein-protein interaction between TRA-2A and FEM-3

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