The N-terminal domain of Sxl protein disrupts Sxl autoregulation in females and promotes female-specific splicing of tra in males

Development. 1999 Jul;126(13):2841-53. doi: 10.1242/dev.126.13.2841.


Sex determination in Drosophila depends upon the post-transcriptional regulatory activities of the Sex-lethal (Sxl) gene. Sxl maintains the female determined state and activates female differentiation pathways by directing the female-specific splicing of Sxl and tra pre-mRNAs. While there is compelling evidence that Sxl proteins regulate splicing by directly binding to target RNAs, previous studies indicate that the two Sxl RNA-binding domains are not in themselves sufficient for biological activity and that an intact N-terminal domain is also critical for splicing function. To further investigate the functions of the Sxl N terminus, we ectopically expressed a chimeric protein consisting of the N-terminal 99 amino acids fused to ss-galactosidase. The Nss-gal fusion protein behaves like a dominant negative, interfering with the Sxl autoregulatory feedback loop and killing females. This dominant negative activity can be attributed to the recruitment of the fusion protein into the large Sxl:Snf splicing complexes that are found in vivo and the consequent disruption of these complexes. In addition to the dominant negative activity, the Nss-gal fusion protein has a novel gain-of-function activity in males: it promotes the female-specific processing of tra pre-mRNAs. This novel activity is discussed in light of the blockage model for the tra splicing regulation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bacterial Proteins / genetics*
  • Drosophila / embryology*
  • Drosophila / genetics
  • Drosophila Proteins*
  • Escherichia coli Proteins*
  • Female
  • Gene Expression Regulation, Developmental
  • Genes, Dominant
  • Genes, Lethal
  • Insect Proteins / metabolism
  • Male
  • RNA Precursors / genetics
  • RNA Processing, Post-Transcriptional
  • RNA Splicing / genetics*
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / genetics*
  • Recombinant Fusion Proteins / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sex Determination Processes
  • Transgenes
  • beta-Galactosidase / genetics


  • Bacterial Proteins
  • Drosophila Proteins
  • Escherichia coli Proteins
  • Insect Proteins
  • RNA Precursors
  • RNA, Messenger
  • RNA-Binding Proteins
  • Recombinant Fusion Proteins
  • Sxl protein, Drosophila
  • kilA protein, E coli
  • beta-Galactosidase