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male development represses nale genes and activates female genes female development

Ft CURE 17-28 A cascade of alternative splicing events determines the sex of a fly.

As described in detail in the text, the Sex-lethal protein is produced in flies that will develop into females (shown on the right of the figure) but not those that will develop into males (shown on the left). The presence of that protein is maintained by autoregulation 0f the splicing of its own message, tn the absence of that regulation no functional protein is produced (in males). Sex-lethal also controls splicing of the tra gene, produong functional Tra protein in females (but not males) Tra ¡s itself a splicing regulator. It acts on pre-mRNA from the double-sex gene. When the dsx mRNA is spliced in response to Tra protein, a version of Doublesex protein is produced (in females) with a stretch of 30 amino acids at its C-termina) end that distinguish it from the form of the protein produced in the absence of the Tra regulator (in males). The female foim of Dsx activates genes required for female development end represses those for male development The male form, which has a stretch Of 150 amino acids ai the C-terminal end, represses genes that direct female development. Sxl protein acts as a splicing repressor by binding to the pyrimidme trac! at the 3' splice site (see Figure 13 2) The Tra protein, in contrast, acts as a splicing activator. It binds to an enhancer sequence in one of the exons of dsx RNA (see Figure 13-13).

Tra protein is also a splicing regulator. Whereas Sxl is a splicing repressor, Tra is an activator (Figure 17-28). One of its targets is RNA made horn the gene encoding Double sex (Dsx). This RNA is spliced in two alternative forms, both encoding regulatory proteins but with different activities. Thus, in the presence of tra, dsx RNA is spliced in a way that gives rise lo a protein that represses expression of male-specific genes, in the absence of Tra protein, the form of Dsx produced represses female-specific genes.

Expression of the Yeast Transcriptional Activator Gcn4 Is Controlled at the Level of Translation

Ccn4 is a yeast transcriptional activator tliat regulates the expression of genes encoding enzymes that direct amino acid biosynthesis. Although i! is a transcriptional activator, Gcn4 is itself regulated at the level of translation, in the presence of low levels of amino acids, the Gcn4 mRNA is translated (and so the bio synthetic enzymes are expressed). In the presence of high levels of amino acids, the Gcn4 mRNA is not translated. How is this regulation achieved?

FIGURE 17-29 Translational control of Gcn4 in response to amino acid starvation.

As described in detail in the text, the open-reading frame encoding the yeast activator Gcn4 is preceeded by four other ORFs. The first of these upstream ORf-s is translated initially When amino aods are scarce (starvation conditions), it takes longer for the translational machinery to re-initiate translation, and so it tends to reach the Gcn4-encoding open-reading frame before re-initiating and translates that to give Gcn4 protein. When amino acids are plentiful (nonstarva tion conditions) re-initiation takes place at intervening Open reading frames, and the translation machinery then dissociates from the RNA template and Gcn4 is never translated. (Source: Hinnebusch A G. 1997. Journal of Biology of the Cell 272 21661-21664, fig. l Copyright © 1997 The American Society tor Biochemistry & Molecular Biology.)

nonstarvation conditions elF2*

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