User:Mark Macbeth/Sandbox2: Difference between revisions

The alternative splicing pathways of Sxl differ, but both involve repression at the 3' splice site<ref name="Handa"/><ref name="Black">. The ''tra'' expression pathway only involves the 3' splice site, while the ''msl-2'' pathway involves both the 3' splice site and the 5' splice site. Both mechanisms cause U2AF binding downstream with lower affinity (Fig. 3)<ref name="Black"/>. U2AF is a more general splicing factor than Sxl, and prefers cytidine-containing poly-uridine pre-mRNA sequences, so Sxl binds to the guanosine-containing pre-mRNA with a 10⁴-fold greater affinity<ref name="Handa"/>.

Sxl is capable of autoregulation of its expression<ref name="Black"/>. The Sxl gene is transcribed in male flies, but the inclusion of exon 3 results in a premature stop codon, producing an inactive, truncated protein. The same Sxl promoter is active in female flies, but an additional (briefly active) Sxl promoter produces a transcript with exon 3 removed, resulting in an active Sxl protein which will initiate other female-specific splicing cascades<ref name="Black"/>.  

In alternative splicing of the ''tra'' gene, Sxl binds at the 3' poly-uridine site (Fig. 3). This causes U2AF to bind downstream and the spliceosome transcribes the following exon<ref name="Penalva"/>. In the absence of Sxl, the normal gene for male development is transcribed. The exon contains a stop codon which results in a truncated, non-functional protein<ref name="Black"/>. In the presence of Sxl, this exon is spliced, so the stop codon is skipped<ref name="Black"/> (Fig. 3). This enables translation of an active ''tra'' protein<ref name="Black"/>.  

The alternative splicing of ''msl-2'' is reliant on Sxl binding to both the 5' and 3' splice sites (Fig. 3). Sxl binds at the 3' splice site, replacing U2AF as in ''tra'' splicing. Sxl also competes with [http://www.uniprot.org/uniprot/Q26281 Rox8], which binds to the first intron. As a result, Sxl prevents splicing of the first intron of the ''msl-2'' primary transcript. Sxl also binds to the poly- U sequences of the 3' UTR to repress translation (Fig.3)<ref name="Panalva">doi:10.1128/mmbr.67.3.343-359.2003</ref>. When Sxl targets ''msl-2'', the first intron is retained<ref name="Black"/>. However, the retained intron is in the [https://en.wikipedia.org/wiki/Untranslated_region 5' UTR] and does not affect the reading frame<ref name="Black"/>.