Tazswana’s Story by S. Catherine Silver Key

Handout 7—Analyzing Tazswana’s Intron

Figure 7-1. Analyzing Tazswana’s intron. In certain β-thalassemias, a base substitution occurs at position 705 in the second intervening sequence (IVS2, intron 2) with a transition from T to G occurring in the DNA. The transition converts the U (underlined, Panel A) in the wild-type IVS2 pre-mRNA to a G (underlined and in boldface, Panel B) in Tazswana’s pre-mRNA. This results in a GU 5′ splice site, called an aberrant splice site, appearing in the middle of intron 2. As a result, another intron sequence that was already present, CAG, will now be used (bolded and italicized in Panel B). Because the site was there, but not recognized, it is called a cryptic splice site.

Questions

1. Comparing and contrasting Tazswana’s pre-mRNA intron to the normal intron, answer the following questions (use terms such as 5′ splice site, 3′ splice site, etc.):
   1. How is Tazswana’s intron similar to the normal β-globin pre-mRNA?
   2. How is Tazswana’s intron different from the normal β-globin pre-mRNA?
2. Assuming that the cellular splicing machinery will recognize sets of “GU” and “CAG” together in the right context as marking the beginning and end of an intron, and that an extra “GU” will be grouped with the next downstream “CAG” as a “complete set,” predict how Tazswana’s pre-mRNA will be processed into mRNA. Show the resulting mRNA sequence from this process.
3. If the doctors could somehow trick the splicesome (the cell’s machinery that splices pre-mRNAs into mRNAs) into ignoring Tazswana’s extra splicing sequence, could she have a normal β-globin mRNA? Explain why or why not.

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