Does mRNA translation starting from an alternative initiation site contribute to the pathology of Huntington's disease?

ABSTRACT

Huntington's disease is associated with an expanded and unstable trinucleotide repeat (CAG)(n). Various possibilities have been suggested to explain the significance of poly-(CAG) length in HD, including changes in the structure of the product (huntingtin) which result in the protein acquiring deleterious properties. We have looked at the nucleotide sequence coding for huntingtin and find that another possibility may exist for the correlation between the occurrence of HD and poly-CAG length. We have noted an alternative reading frame that includes the trinucleotide repeat, now read as (GCA)(n). Upon close examination of this alternative gene product, we observe features that suggest it can likewise have deleterious properties.