Gene Symbol: tra2
Description: transformer 2
Alias: CG10128, Dmel\CG10128, TRA 2, TRA-2, TRA2, Tra-2, Tra2, tra-2, transformer 2, CG10128-PA, CG10128-PB, CG10128-PC, CG10128-PD, CG10128-PE, CG10128-PF, CG10128-PG, Transformer-2, tra2-PA, tra2-PB, tra2-PC, tra2-PD, tra2-PE, tra2-PF, tra2-PG, transformer2
Species: fruit fly

Top Publications

  1. Saccone G, Salvemini M, Pane A, Polito L. Masculinization of XX Drosophila transgenic flies expressing the Ceratitis capitata DoublesexM isoform. Int J Dev Biol. 2008;52:1051-7 pubmed publisher
  2. Sciabica K, Hertel K. The splicing regulators Tra and Tra2 are unusually potent activators of pre-mRNA splicing. Nucleic Acids Res. 2006;34:6612-20 pubmed a binding platform for the cooperative assembly of a heterotrimeric complex consisting of the SR proteins Tra, Tra2 and 9G8...
  3. Tian M, Maniatis T. A splicing enhancer exhibits both constitutive and regulated activities. Genes Dev. 1994;8:1703-12 pubmed
    The Drosophila proteins Transformer (Tra) and Transformer2 (Tra2) regulate the sex-specific alternative splicing of Drosophila doublesex (dsx) pre-mRNA by specifically binding to a splicing enhancer (dsx repeat element; dsxRE) located 300 ..
  4. Lynch K, Maniatis T. Synergistic interactions between two distinct elements of a regulated splicing enhancer. Genes Dev. 1995;9:284-93 pubmed
    ..studies have shown that the activity of the dsxRE requires the splicing regulators Transformer (Tra) and Transformer 2 (Tra2), and one or more members of the SR family of general splicing factors...
  5. Belote J, Baker B. Sexual behavior: its genetic control during development and adulthood in Drosophila melanogaster. Proc Natl Acad Sci U S A. 1987;84:8026-30 pubmed
  6. Hertel K, Lynch K, Hsiao E, Liu E, Maniatis T. Structural and functional conservation of the Drosophila doublesex splicing enhancer repeat elements. RNA. 1996;2:969-81 pubmed
    ..sequence conservation was demonstrated by showing that the two enhancers are functionally interchangeable in Tra-/Tra2-dependent in vitro splicing...
  7. Ruiz M, Sanchez L. Effect of the gene transformer of Anastrepha on the somatic sexual development of Drosophila. Int J Dev Biol. 2010;54:627-33 pubmed publisher
    ..on the dose of Anastrepha tra and Drosophila transformer-2 (tra-2) genes, and that the Anastrepha Tra-Drosophila Tra2 complex is not as efficient as the Drosophila Tra-Tra2 complex at inducing the female-specific splicing of ..
  8. Blencowe B. Exonic splicing enhancers: mechanism of action, diversity and role in human genetic diseases. Trends Biochem Sci. 2000;25:106-10 pubmed
    ..Ominously, these latter studies predict that many human genetic diseases linked to mutations within exons might be caused by the inactivation of ESEs. ..
  9. Amrein H, Maniatis T, Nothiger R. Alternatively spliced transcripts of the sex-determining gene tra-2 of Drosophila encode functional proteins of different size. EMBO J. 1990;9:3619-29 pubmed
    ..Sequence analysis of two temperature-sensitive mutations provides evidence that the RNP motif represents an important functional domain of the tra-2 protein. ..

More Information


  1. Bray S, Amrein H. A putative Drosophila pheromone receptor expressed in male-specific taste neurons is required for efficient courtship. Neuron. 2003;39:1019-29 pubmed
  2. Mattox W, Baker B. Autoregulation of the splicing of transcripts from the transformer-2 gene of Drosophila. Genes Dev. 1991;5:786-96 pubmed
    ..The finding that transformer-2 controls multiple splicing decisions suggests that a variety of different alternative splicing choices could be regulated by a relatively limited number of trans-acting factors. ..
  3. Kumar S, Lopez A. Negative feedback regulation among SR splicing factors encoded by Rbp1 and Rbp1-like in Drosophila. EMBO J. 2005;24:2646-55 pubmed
    ..These results provide the first example of a feedback-regulated SR protein network with evidence of an active homeostatic role for alternative isoforms. ..
  4. Heinrichs V, Baker B. The Drosophila SR protein RBP1 contributes to the regulation of doublesex alternative splicing by recognizing RBP1 RNA target sequences. EMBO J. 1995;14:3987-4000 pubmed
    ..Moreover, our studies reveal that RBP1 contributes to the activation of female-specific dsx splicing in vivo by recognizing the RBP1 target sequences within the purine-rich polypyrimidine tract of the female-specific 3' splice site. ..
  5. Bownes M. The regulation of the yolk protein genes, a family of sex differentiation genes in Drosophila melanogaster. Bioessays. 1994;16:745-52 pubmed
  6. Lopez A. Alternative splicing of pre-mRNA: developmental consequences and mechanisms of regulation. Annu Rev Genet. 1998;32:279-305 pubmed
    ..Cooperative and antagonistic effects integrated at regulatory elements are likely to be important for specificity and for finely tuned differences in cell-type-specific alternative splicing patterns. ..
  7. Sanchez L, Gorfinkiel N, Guerrero I. Sex determination genes control the development of the Drosophila genital disc, modulating the response to Hedgehog, Wingless and Decapentaplegic signals. Development. 2001;128:1033-43 pubmed
    ..A model is presented for the dimorphic sexual development of the genital primordium in which both Doublesex(M) and Doublesex(F) products play positive and negative roles. ..
  8. Amrein H, Hedley M, Maniatis T. The role of specific protein-RNA and protein-protein interactions in positive and negative control of pre-mRNA splicing by Transformer 2. Cell. 1994;76:735-46 pubmed
    We have investigated the function of different structural domains of the Drosophila splicing regulator Transformer 2 (Tra2)...
  9. Hertel K, Maniatis T. The function of multisite splicing enhancers. Mol Cell. 1998;1:449-55 pubmed
    ..Thus, the function of multisite enhancer elements to increase the probability of an interaction between the enhancer complex and the splicing machinery rather than to promote functional synergy. ..
  10. Baker B. Sex in flies: the splice of life. Nature. 1989;340:521-4 pubmed
  11. Pomiankowski A, Nöthiger R, Wilkins A. The evolution of the Drosophila sex-determination pathway. Genetics. 2004;166:1761-73 pubmed
    ..Our hypothesis is built on the available data from Drosophila and other insect species, and we point out where it is amenable to further experimental and comparative tests. ..
  12. Casper A, Van Doren M. The control of sexual identity in the Drosophila germline. Development. 2006;133:2783-91 pubmed
    ..Here, we explore how sexual identity is established in the Drosophila germline, how this affects other aspects of germ cell development and what studies in Drosophila can teach us about mammalian germ cells. ..
  13. McGuffin M, Chandler D, Somaiya D, Dauwalder B, Mattox W. Autoregulation of transformer-2 alternative splicing is necessary for normal male fertility in Drosophila. Genetics. 1998;149:1477-86 pubmed
    ..Our results suggest that autoregulation of TRA-2(226) expression in male germ cells is necessary for normal spermatogenesis. ..
  14. Chandler D, McGuffin M, Piskur J, Yao J, Baker B, Mattox W. Evolutionary conservation of regulatory strategies for the sex determination factor transformer-2. Mol Cell Biol. 1997;17:2908-19 pubmed
    ..melanogaster and D. virilis is accomplished under the control of similar regulatory pathways...
  15. Lynch K, Maniatis T. Assembly of specific SR protein complexes on distinct regulatory elements of the Drosophila doublesex splicing enhancer. Genes Dev. 1996;10:2089-101 pubmed
    ..Here, we show that the Drosophila regulatory proteins Transformer (Tra) and Transformer 2 (Tra2) recruit different members of the SR family of splicing factors to the repeats and the PRE...
  16. Salz H. Sex determination in insects: a binary decision based on alternative splicing. Curr Opin Genet Dev. 2011;21:395-400 pubmed publisher
    ..Studies exploring the mechanisms of sex-specific splicing have revealed the extent to which sex determination is integrated with other developmental regulatory networks. ..
  17. Hoshijima K, Inoue K, Higuchi I, Sakamoto H, Shimura Y. Control of doublesex alternative splicing by transformer and transformer-2 in Drosophila. Science. 1991;252:833-6 pubmed
    ..Furthermore, analyses of mutant constructs of dsx showed that a portion of the female-specific exon sequence was required for regulation of dsx pre-messenger RNA splicing. ..
  18. Billeter J, Rideout E, Dornan A, Goodwin S. Control of male sexual behavior in Drosophila by the sex determination pathway. Curr Biol. 2006;16:R766-76 pubmed
  19. Dauwalder B, Tsujimoto S, Moss J, Mattox W. The Drosophila takeout gene is regulated by the somatic sex-determination pathway and affects male courtship behavior. Genes Dev. 2002;16:2879-92 pubmed
    ..Expression analysis of a subset of these genes suggests that the takeout gene family encodes multiple factors with sex-specific functions. ..
  20. Graham P, Penn J, Schedl P. Masters change, slaves remain. Bioessays. 2003;25:1-4 pubmed
    ..DmSxl controls the alternative splicing of a downstream gene, transformer (tra), which acts with tra2 to control alternative splicing of doublesex (dsx)...
  21. Tian M, Maniatis T. Positive control of pre-mRNA splicing in vitro. Science. 1992;256:237-40 pubmed
    ..Therefore, Tra and Tra-2 may act by promoting the assembly of a multiprotein complex on the exon sequence. This complex may facilitate recognition of the adjacent 3' splice site by the splicing machinery. ..
  22. Baker B, Ridge K. Sex and the single cell. I. On the action of major loci affecting sex determination in Drosophila melanogaster. Genetics. 1980;94:383-423 pubmed
    ..Implications of these observations for the function of other homeotic loci are discussed. ..
  23. Ryner L, Baker B. Regulation of doublesex pre-mRNA processing occurs by 3'-splice site activation. Genes Dev. 1991;5:2071-85 pubmed
    ..Regulated polyadenylation was obtained only in the presence of splicing, suggesting that activation of female-specific exon use occurs by 3'SS activation. ..
  24. Belote J, Baker B. The dual functions of a sex determination gene in Drosophila melanogaster. Dev Biol. 1983;95:512-7 pubmed
    ..Orcein-stained testis preparations from tra-2 males reveal a spermiogenic defect similar to that associated with dominant male sterile (X; autosome) translocations. ..
  25. Manoli D, Foss M, Villella A, Taylor B, Hall J, Baker B. Male-specific fruitless specifies the neural substrates of Drosophila courtship behaviour. Nature. 2005;436:395-400 pubmed
    ..Together, these data demonstrate that FruM proteins specify the neural substrates of male courtship. ..
  26. Qi J, Su S, McGuffin M, Mattox W. Concentration dependent selection of targets by an SR splicing regulator results in tissue-specific RNA processing. Nucleic Acids Res. 2006;34:6256-63 pubmed
    The splicing factor Transformer-2 (Tra2) is expressed almost ubiquitously in Drosophila adults, but participates in the tissue-specific regulation of splicing in several RNAs...
  27. Usui Aoki K, Ito H, Ui Tei K, Takahashi K, Lukacsovich T, Awano W, et al. Formation of the male-specific muscle in female Drosophila by ectopic fruitless expression. Nat Cell Biol. 2000;2:500-6 pubmed
  28. Smith C, Valcarcel J. Alternative pre-mRNA splicing: the logic of combinatorial control. Trends Biochem Sci. 2000;25:381-8 pubmed
    ..Its modulation is achieved through the combinatorial interplay of positive and negative regulatory signals present in the RNA, which are recognized by complexes composed of members of the hnRNP and SR protein families. ..
  29. Dauwalder B, Mattox W. Analysis of the functional specificity of RS domains in vivo. EMBO J. 1998;17:6049-60 pubmed
    ..These results indicate that RS domains are not all functionally equivalent in vivo. ..
  30. Arthur B, Jallon J, Caflisch B, Choffat Y, Nothiger R. Sexual behaviour in Drosophila is irreversibly programmed during a critical period. Curr Biol. 1998;8:1187-90 pubmed
    ..We conclude that sexual behaviour is irreversibly programmed during a critical period as a result of the activity or inactivity of a single control gene. ..
  31. Chandler D, Qi J, Mattox W. Direct repression of splicing by transformer-2. Mol Cell Biol. 2003;23:5174-85 pubmed
    The Drosophila melanogaster sex determination factor Tra2 positively regulates the splicing of both doublesex (dsx) and fruitless (fru) pre-mRNAs but negatively affects the splicing of the M1 intron in tra2 pre-mRNA...
  32. Ryner L, Goodwin S, Castrillon D, Anand A, Villella A, Baker B, et al. Control of male sexual behavior and sexual orientation in Drosophila by the fruitless gene. Cell. 1996;87:1079-89 pubmed
  33. Hedley M, Maniatis T. Sex-specific splicing and polyadenylation of dsx pre-mRNA requires a sequence that binds specifically to tra-2 protein in vitro. Cell. 1991;65:579-86 pubmed
    ..These observations suggest that tra-2 is a positive regulator of dsx pre-mRNA processing. ..
  34. Belote J, Baker B. Sex determination in Drosophila melanogaster: analysis of transformer-2, a sex-transforming locus. Proc Natl Acad Sci U S A. 1982;79:1568-72 pubmed
    ..These and other results support the model that the tra-2+ and tra+ loci act to control the expression of the bifunctional doublesex (dsx) locus. ..
  35. Hall J. The mating of a fly. Science. 1994;264:1702-14 pubmed
    ..Further behavioral mutations seemed originally to be courtship-specific, turned out not to have that property, and have led to a broadened perspective on the nature and action of Drosophila's sex-determination genes. ..
  36. Tian M, Maniatis T. A splicing enhancer complex controls alternative splicing of doublesex pre-mRNA. Cell. 1993;74:105-14 pubmed
    ..splicing of Drosophila doublesex (dsx) pre-mRNA is regulated by the products of the transformer (tra) and transformer 2 (tra2) genes...
  37. Cline T, Meyer B. Vive la différence: males vs females in flies vs worms. Annu Rev Genet. 1996;30:637-702 pubmed
    ..Although no overlap has been found among the molecules used by flies and worms to achieve sex determination, striking similarities have been found in the genetic strategies used by these two species to differentiate their sexes. ..
  38. Dauwalder B, Amaya Manzanares F, Mattox W. A human homologue of the Drosophila sex determination factor transformer-2 has conserved splicing regulatory functions. Proc Natl Acad Sci U S A. 1996;93:9004-9 pubmed
  39. Mattox W, Palmer M, Baker B. Alternative splicing of the sex determination gene transformer-2 is sex-specific in the germ line but not in the soma. Genes Dev. 1990;4:789-805 pubmed
    ..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. ..
  40. Chandler D, McGuffin M, Mattox W. Functionally antagonistic sequences are required for normal autoregulation of Drosophila tra-2 pre-mRNA splicing. Nucleic Acids Res. 2001;29:3012-9 pubmed
    ..Our results indicate that antagonistic elements in the M1 intron act together to establish a context that is permissive for repression of splicing by TRA-2 while allowing efficient splicing in the absence of a repressor. ..
  41. Lazareva A, Roman G, Mattox W, Hardin P, Dauwalder B. A role for the adult fat body in Drosophila male courtship behavior. PLoS Genet. 2007;3:e16 pubmed
    ..In support of this idea, we demonstrate that Takeout, a protein known to influence mating, is present in the hemolymph of adult males but not females and acts as a secreted protein. ..
  42. Fortier E, Belote J. Temperature-dependent gene silencing by an expressed inverted repeat in Drosophila. Genesis. 2000;26:240-4 pubmed
    ..Moreover, by altering the dosage of either the transgenes or the endogenous tra2(+) loci, one can vary the effect over a wide range of mutant phenotypes.
  43. Unni E, Su S, Zraly C, Mattox W. Analysis of a null mutation in the Drosophila splicing regulator Tra2 suggests its function is restricted to sexual differentiation. Genesis. 2003;37:76-83 pubmed
    b>Tra2 is a regulator of pre-mRNA splicing and a key component of the Drosophila somatic sex determination pathway...
  44. Heinrichs V, Ryner L, Baker B. Regulation of sex-specific selection of fruitless 5' splice sites by transformer and transformer-2. Mol Cell Biol. 1998;18:450-8 pubmed
  45. Qi J, Su S, Mattox W. The doublesex splicing enhancer components Tra2 and Rbp1 also repress splicing through an intronic silencer. Mol Cell Biol. 2007;27:699-708 pubmed publisher
    ..and fruitless pre-mRNAs has been well studied and depends on the serine-arginine-rich (SR) splicing factors Tra, Tra2, and Rbp1. Little is known, however, about how SR factors negatively regulate splice sites in other RNAs...
  46. Lam B, Bakshi A, Ekinci F, Webb J, Graveley B, Hertel K. Enhancer-dependent 5'-splice site control of fruitless pre-mRNA splicing. J Biol Chem. 2003;278:22740-7 pubmed
    ..Alternative splicing of fru is regulated by TRA and TRA2 and depends on an exonic splicing enhancer (fruRE) consisting of three 13-nucleotide repeat elements, nearly ..
  47. Mattox W, McGuffin M, Baker B. A negative feedback mechanism revealed by functional analysis of the alternative isoforms of the Drosophila splicing regulator transformer-2. Genetics. 1996;143:303-14 pubmed
    ..This isoform appears to regulate its own synthesis during spermatogenesis through a negative feedback mechanism involving intron retention. ..
  48. Monsma S, Wolfner M. Structure and expression of a Drosophila male accessory gland gene whose product resembles a peptide pheromone precursor. Genes Dev. 1988;2:1063-73 pubmed
    ..The predicted sequence of one protein has features of a peptide hormone precursor, and a region in which 11 of 17 amino acids are identical to egg-laying hormone (ELH) of the California sea hare, Aplysia californica. ..
  49. Kraus K, Lee Y, Lis J, Wolfner M. Sex-specific control of Drosophila melanogaster yolk protein 1 gene expression is limited to transcription. Mol Cell Biol. 1988;8:4756-64 pubmed
    ..One of these vectors is designed so that the heat-induced transcript produced is the "authentic" primary transcript; it should be useful for studies of posttranscriptional regulation. ..
  50. Baker B, Hoff G, Kaufman T, Wolfner M, Hazelrigg T. The doublesex locus of Drosophila melanogaster and its flanking regions: a cytogenetic analysis. Genetics. 1991;127:125-38 pubmed
    ..It is suggested that the lack of essential genes in this region is due to the region (1) containing genes with nonessential functions and (2) being duplicated, possibly both internally and elsewhere in the genome. ..
  51. Oliver B, Kim Y, Baker B. Sex-lethal, master and slave: a hierarchy of germ-line sex determination in Drosophila. Development. 1993;119:897-908 pubmed
    ..The fused+, ovarian tumor+, ovo+ and sans fille+ genes function upstream of Sex-lethal+ in the germ line. ..
  52. Madigan S, Edeen P, Esnayra J, McKeown M. att, a target for regulation by tra2 in the testes of Drosophila melanogaster, encodes alternative RNAs and alternative proteins. Mol Cell Biol. 1996;16:4222-30 pubmed
    ..differs from somatic RNAs in both promoter usage and RNA processing and is dependent on the function of the transformer 2 gene. The differences between the somatic and testis RNAs have substantial consequences at the protein level...
  53. Zhao Y, Cocco C, Domenichini S, Samson M, Rabinow L. The IMD innate immunity pathway of Drosophila influences somatic sex determination via regulation of the Doa locus. Dev Biol. 2015;407:224-31 pubmed publisher
  54. Vincent S, Perkins L, Perrimon N. Doublesex surprises. Cell. 2001;106:399-402 pubmed
  55. Zarkower D. Establishing sexual dimorphism: conservation amidst diversity?. Nat Rev Genet. 2001;2:175-85 pubmed
    ..Studies of sex-determining mechanisms are beginning to reveal how sexual dimorphism arises and evolves. ..
  56. Peng X, Mount S. Genetic enhancement of RNA-processing defects by a dominant mutation in B52, the Drosophila gene for an SR protein splicing factor. Mol Cell Biol. 1995;15:6273-82 pubmed
    ..Reversion of the B52ED dominant allele with X rays led to the isolation of a B52 null allele. Together, these results indicate a critical role for the SR protein B52 in pre-mRNA splicing in vivo. ..
  57. Feng Y, Schiff N, Cavener D. Organ-specific patterns of gene expression in the reproductive tract of Drosophila are regulated by the sex-determination genes. Dev Biol. 1991;146:451-60 pubmed
    ..melanogaster, suggesting that the interspecific variation in Gld expression may result from variation in the expression of the sex-determination genes. ..
  58. Taylor B, Truman J. Commitment of abdominal neuroblasts in Drosophila to a male or female fate is dependent on genes of the sex-determining hierarchy. Development. 1992;114:625-42 pubmed
    ..Neuroblasts become determined to adopt a male or female state at the end of the first larval instar, a time when abdominal neuroblasts enter their first postembryonic S-phase. ..
  59. Amrein H, Gorman M, Nothiger R. The sex-determining gene tra-2 of Drosophila encodes a putative RNA binding protein. Cell. 1988;55:1025-35 pubmed
    ..In both sexes, a low level of transcript is present in the soma and a high level in the germ line. This indicates that tra-2 is regulated in a way different from other sex-determining genes. ..