The Questions of Developmental Biology

Maintenance of sxl function
Shortly after Sxl transcription has taken place, a second, "late" promoter on the Sex-lethal
gene is activated, and the gene is now transcribed in both males and females. However, analysis
of the cDNA from Sxl mRNA shows that the Sxl mRNA of males differs from sxl mRNA of
females (Bell et al. 1988). This difference is the result of differential RNA processing.
Moreover, the Sxl protein appears to bind to its own mRNA precursor to splice it in the female
manner. Since males do not have any available Sxl protein when the late promoter is activated,
their new Sxl transcripts are processed in the male manner (Keyes et al. 1992). The male Sxl
mRNA is nonfunctional. While the female-specific Sxl message encodes a protein of 354 amino
acids, the male-specific Sxl transcript contains a translation termination codon (UGA) after amino
acid 48. The differential RNA processing that puts this termination codon into the male-specific
mRNA is shown in Figures 17.17B and 17.18. In males, the nuclear transcript is spliced in a
manner that yields eight exons, and the termination codon is within exon 3. In females, RNA
processing yields only seven exons, and the male-specific exon 3 is now spliced out as a large
intron. Thus, the female-specific mRNA lacks the termination codon.
The protein made by the female-specific Sxl transcript contains two regions that are
important for binding to RNA. These regions are similar to regions found in nuclear RNAbinding
proteins. Bell and colleagues (1988) have shown that there are two targets for the femalespecific
Sxl protein. One of these targets is the pre-mRNA of Sxl itself. The second is the premRNA
of the next gene on the pathway, transformer.
The transformer genes
The Sxl gene regulates somatic sex determination by controlling the processing of the
transformer (tra) gene transcript. The tra message is alternatively spliced to create a femalespecific
mRNA as well as a nonspecific mRNA that is found in both females and males. Like the
male sxl message, the nonspecific tra mRNA contains a termination codon early in the message,
making the protein nonfunctional (Boggs et al. 1987). In tra, the second exon of the nonspecific
mRNA has the termination codon. This exon is not utilized in the female-specific message (see
Figure 17.18). How is it that the females make a different transcript than the males? The femalespecific
protein from the Sxl gene activates a female-specific 3´ splice site in the transformer premRNA,
causing it to be processed in a way that splices out the second exon.