RNA Splicing Defects and Blindness

Retinitis pigmentosa is a degenerative disease of the retina characterized by loss of the light-sensing photoreceptor cells and black mottling of the retina. Several mutations associated with the development of retinitis pigmentosa have been found in factors that mediate splicing of mRNA. For example, inherited missense mutations in the gene encoding the human protein PRP31 result in an autosomal dominant form of the disease. The PRP31 protein promotes assembly of the PRP31–U4–15.5K trimeric complex, which is essential for correct splicing of mRNA. The two PRP31 missense mutations, A194P and A216E, are believed to lead to interference with formation of the trimeric complex, thus preventing proper binding of the spliceosome to mRNA to facilitate intron removal. Loss of PRP31-mediated RNA splicing in photoreceptor cells leads to cell death and vision loss.

Copyright WW Norton & Company, Inc., Miesfeld & McEvoy Biochemistry, 2021
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