Disease relevance of tra-2

• The feminization phenotype induced by deletion of the rpn-10 gene was rescued by knockdown of tra-2, one of sexual fate decision genes promoting female development, and its downstream target tra-1, indicating that the TRA-2-mediated sex determination pathway is crucial for the Deltarpn-10-induced sterile phenotype [1].
• Our data indicate that the regulation of the hermaphrodite germline sex determination pathway at the level of FOG-2/GLD-1/tra-2 mRNA is fundamentally different between C. elegans and C. briggsae, providing functional evidence in support of the independent evolution of self-fertile hermaphroditism [2].

High impact information on tra-2

• Comparisons of GLD-1-mediated translational control of rme-2 and tra-2 suggests that the mechanisms may differ for distinct target mRNA species [3].
• Previous work identified tra-2 as a GLD-1 target for germ line sex determination [3].
• In C. elegans, tra-2 mRNA nuclear export is controlled by a 3'UTR element, the TRE [4].
• Classical genetic studies placed tra-1 as the terminal regulator of the pathway with tra-2 acting upstream as a regulator of regulators of tra-1 [5].
• Genetic analysis of tra-3 has suggested that its product may act as a potentiator of another sex determination gene, tra-2 [6].

Biological context of tra-2

• We employed RNA interference to show that in all three species, the male-promoting function of fem-3 and its epistatic relationship with its female-promoting upstream repressor, tra-2, are conserved [7].
• The tra-2 and tra-3 genes act as negative regulators of the fem genes and fog-1 to allow oogenesis [8].
• Male sex determination in the Caenorhabditis elegans hermaphrodite germline requires translational repression of tra-2 mRNA by the GLD-1 RNA binding protein [9].
• In this paper we report the cDNA sequence corresponding to a 4.7 kb tra-2 mRNA and show that it is composed of 23 exons, is trans-spliced to SL2, and contains a perfect direct repeat in the 3' untranslated region [10].
• tra-2 encodes a membrane protein and may mediate cell communication in the Caenorhabditis elegans sex determination pathway [10].

Anatomical context of tra-2

• Dominant, gain-of-function tra-2 mutations have now been isolated that completely feminize the germline of XX animals so that they make only oocytes and no sperm and, thus, are female [11].

Regulatory relationships of tra-2

• In XO animals, tra-2 is negatively regulated by her-1, which acts cell nonautonomously [10].

Other interactions of tra-2

• These fall into three autosomal complementation groups, termed tra-1, tra-2, and tra-3 [12].
• We cloned fog-2 by finding that its gene product physically interacts with GLD-1, forming a FOG-2/GLD-1/tra-2 3'untranslated region ternary complex [9].
• If so, then regulation of sexual fate by her-1 and tra-2 might provide a general model for the coordination of groups of cells to follow a single cell fate [10].

Analytical, diagnostic and therapeutic context of tra-2

• The tra-2 region is delineated by mapping Southern blot differences associated with 11 tra-2 mutations, mutant rescue, and analysis of tra-2 RNAs [13].
• Another, the DRE/TGE element of the tra-2 3' UTR, was not detected by sequence analysis [14].

References