Drosophila Sex-Lethal (Sxl) protein

The presence or absence of Sxl in an early embryo will determine whether it develops as a male or a female.

Sex-lethal is a sequence-specific RNA binding protein that recognizes a specific UGUUUUUUU element in its target RNAs. It has a Β1,2,3 & 4 domains as well as RNA recognition motifs RRM1 and RRM2.

Female embryo

Early female embryo

There is transcription from the Sxl P_E promoter. An mRNA is encoded starting at the E1 exon. A functional Sxl protein is expressed.

Late female embryo

The P_L promoter is activated. Its ORF is different than P_E and L3 now has a premature stop codon. However, Sxl^early binds near L3 to block U2Af from binding the 3' splice site. Thus L3 (and its stop codon) is skipped in females. Functional Sxl is expressed.

Male embryo

Early male embryo

No transcription from P_E. No Sxl expressed.

Late male embryo

The P_L promoter is activated. There is no Sxl^early, so the stop codon in L3 leads to expression of a truncated and inactive Sxl.

Sxl and Tra

The female produced Sex-lethal protein also regulates splicing of Transformer (Tra), the next gene downstream in the Sexual Differentiation Pathway.

An exon in Tra pre-mRNA has two 3’ splice sites. U2AF has higher affinity for the primary upstream 3’ splice site, so splicing occurs there. However, this polypyrimidine tract also contains a high affinity Sxl binding element allowing Sxl to bind if it is present.