Question: What other diseases can be caused by the cell incorrectly splicing?

Judith Sleeman answered on 19 Jun 2012:

There are many ways that problems with splicing can lead to illness. Many mutations that result in cells not having proteins they need actually affect the way the RNA from a particular gene is spliced. This can make the mRNA unstable so it gets destroyed and the cell can’t make any proteins from it, or can make an mRNA with the wrong sequence that makes a faulty protein.

A classic example of a disease caused by a splicing defect is beta thalassemia, which is an inherited form of anemia. The beta chain of haemaglobin (the protein in red blood cells that carries oxygen) is made wrongly in people with beta thalassemia because of a mistake in the sequences that are needed for proper mRNA splicing, so their blood can’t carry enough oxygen.

Looking a bit wider, we’re not yet sure if a cell just being a bit rubbish at splicing all of its mRNAs can lead to disease. Problems in the splicing of lots of genes have been seen in mouse models of the neurodegenerative condition, Spinal Muscular Atrophy, so it might be that faulty splicing causes SMA. However, we don’t yet know this for sure. It could be that faulty splicing is just something that happens in the cells of people with SMA and something else causes the symptoms of the disease. Mutations in proteins needed for mRNA splicing have been seen in some other diseases as well, mostly degenerative diseases, so it is quite likely that general problems with splicing can cause illness.