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20 May, 14:26

Smilin is a (hypothetical) protein that causes people to be happy. It is inactive in many chronically unhappy people. The mRNA isolated from a number of different unhappy persons in the same family was found to lack an internal stretch of 173-nucleotides that are present in the Smilin mRNA isolated from a control group of generally happy people. The DNA sequences of the Smilin genes from the happy and unhappy persons were determined and compared. They differed by just one nucleotide change---and no nucleotides were deleted. Moreover, the change was found in an intron. Can you hypothesize a molecular mechanism by which a single nucleotide change in a gene could cause the observed internal deletion in the mRNA? Be sure to include a comparison of the mechanism that is involved between what happens in the normal and mutant transcript. What consequences for the Smilin protein would result from removing a 173-nucleotide-long internal stretch from the coding region of the Smiling mRNA?

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  1. 20 May, 14:28
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    The single nucleotide mutation affects the splicing of the mRNA molecule of Smilin in unhappy people. This with result in a truncated protein lacking part of it amino acidic chain

    Explanation:

    It's true that the information of aminoacids that form the proteins is codified on the exons, but introns also have important information, for example, the sequences related to the splicing of the mRNA exons.

    Briefly, during the splicing process, the introns are removed, leaving the mRNA that is going to be translated (there could be also other post translational modifications before going to ribosomes).

    Also, there's different ways to splice the different exons. For example, let's say a mRNA has four exons, so the mature mRNA could have exons 1-2-3-4, or 1-2-4, or 1-2-3, it depends on the location of the splicing signals. This are called splicing alternatives, so the same original mRNA can give arise to different forms of a protein.

    In the particular case of Smilin, apparently the DNA has a single mutation in the intron for the mRNA of the protein. Despite it might seem as a minor difference, it causes the final mRNA (the one that is translated) to lose an internal stretch of 173 nucleotides.

    A possible explanation is that this single mutation is affecting a splicing signaling sequence, making the splicing complexes skip one exon. Again, if we imagine that the original protein has four exons, this means that the happy people has an mRNA with all the exons, while unhappy people is lacking one.

    As a result, the protein Smilin will be lacking part of its internal region. The actual effects this has on the protein function will depend on the role of the deleted section.
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