Disease relevance of tra

• Feminization of parts of the antennal lobe and mushroom body by targeted expression of a female-determining gene transformer+ (tra+) drives the male to court other males [1].
• Mutations in the tra target gene fruitless (fru), which is expressed in the antennal lobe as well as the suboesophageal ganglion (the gustatory inputs are processed here), also induce homosexual courtship in males [1].

High impact information on tra

• Although all sexually dimorphic characteristics in Drosophila were thought to be controlled by the sex determination pathway through the gene transformer (tra), the expression of roX1 is independent of tra activity [2].
• We find that Tra2 interacts with itself, with the splicing regulator Transformer, and with the general splicing factor SF2 in vitro and in the yeast two-hybrid system [3].
• Arginine/serine-rich domains of the su(wa) and tra RNA processing regulators target proteins to a subnuclear compartment implicated in splicing [4].
• By site-directed mutagenesis, we determined that the 70K protein consists of 437 amino acids (52 kd), and found that its aberrant electrophoretic migration is due to a carboxy-terminal charged domain structurally similar to two Drosophila proteins (su(wa) and tra) that may regulate alternative pre-messenger RNA splicing [5].
• We have examined the effects of mutants in other regulatory genes controlling sexual differentiation on the patterns of processing of the tra and dsx RNA transcripts [6].

Biological context of tra

• The female-specific expression of this gene's function is regulated by the Sex lethal (Sxl) gene, through a mechanism involving sex-specific alternative splicing of tra pre-mRNA [7].
• Here we report the results from an evolutionary approach to investigate tra regulation and function, by isolating the tra-homologous genes from selected Drosophila species, and then using the interspecific DNA sequence comparisons to help identify regions of functional significance [7].
• In first instar larvae with two X chromosomes, XX germ cells enter the female or the male pathway depending on the presence or absence of transformer (tra) activity in the surrounding soma [8].
• The female-specific expression of the tra gene, previously inferred from genetic observations, is based on sex-specific alternative splicing of tra pre-mRNA and is not the result of sex-specific transcriptional activation [9].
• However, expression of mini-white, the marker gene used in both P[GAL4] and P[UAS(G)] constructs, also induces males to court other males, questioning whether GAL4-mediated tra expression alone can induce bisexual behavior [10].

Anatomical context of tra

• If, however, female-specific tra functions are expressed in these animals, XX germ cells become oogenic [8].
• Except for tra, which transforms diplo-X flies so that they look and function like normal males, these mutations do not have the same effect on pheromone-producing tissues and the central nervous system as they do on the appearance of the fly [11].
• Chromosomal females homozygous for tra or tra-2 have no detectable hemolymph vitellogenins, while those homozygous for tra-2OTF exhibit appreciable levels of these proteins [12].

Associations of tra with chemical compounds

• Transcription of the genes is regulated by the genes tra, tra-2 and dsx and also by the insect hormones, juvenile hormone and 20-hydroxyecdysone [13].
• Thus, the hemolymph vitellogenins serve as an easily detectable sexually dimorphic biochemical marker.--We have examined hemolymph vitellogenins by SDS polyacrylamide gel electrophoresis in flies carrying various sex-transformation mutants (dsx, tra, tra-2 and tra-2OTF) singly and in all possible combinations [12].
• Sxl binds to a specific uridine-rich sequence which is believed to be the major cis-acting element for the splicing regulation of the transformer (tra) mRNA precursor [14].

Physical interactions of tra

• Moreover, we find that female Sxl-encoded protein binds specifically to the tra transcript at or near the non-sex-specific acceptor site, implying that the female Sxl gene product is the trans-acting factor that regulates the alternative splicing [15].

Regulatory relationships of tra

• We suggest that tra-2 activity in somatic tissues is regulated through a post-translational sex-specific interaction with the product of the tra gene rather than through the expression of a female-specific tra-2 polypeptide [16].
• In somatic cells, the product of tra regulates the expression of the gene double sex (dsx) which can form a male-specific or a female-specific product [8].
• We suggest a mechanism by which Sex-lethal controls itself and tra [17].

Other interactions of tra

• We show that mutations in the Drosophila LAMMER kinase, Doa, alter sexual differentiation and interact synergistically with tra and tra2 mutations [18].
• We asked whether ectopic somatic expression of the female products of the tra and dsx genes could feminize the germline of XY animals [19].
• The mechanisms of this process were investigated using an in vitro system in which recombinant TRA/TRA2 could activate the female-specific 5'-splice site of fru [20].
• The Drosophila fl(2)d gene, required for female-specific splicing of Sxl and tra pre-mRNAs, encodes a novel nuclear protein with a HQ-rich domain [21].
• The Hudson, Kreitman, and Aguade test rejected a neutral model when the tra region was compared to the 5'-flanking region of alcohol dehydrogenase (Adh) [22].

Analytical, diagnostic and therapeutic context of tra

• In addition, using RT-PCR, we reveal the presence of female transcripts of doublesex and fruitless in the brains of otherwise male (XY) flies exhibiting P[GAL4]-directed tra-expression, demonstrating that P[GAL4]-directed tra is functional at the molecular level [10].
• We have cloned the tra region by microdissection and chromosomal walking [23].
• The sex-determining gene tra of Drosophila: molecular cloning and transformation studies [23].

References