Alternative splicing (AS) appears to be altered in Huntington's disease (HD), but its significance for early, pre-symptomatic disease stages has not been inspected. Here, taking advantage of Htt CAG knock-in mouse in vitro and in vivo models, we demonstrate a correlation between Htt CAG repeat length and increased aberrant linear AS, specifically affecting neural progenitors and, in vivo, the striatum prior to overt behavioral phenotypes stages. Remarkably, a significant proportion (36%) of the aberrantly spliced isoforms are not-functional and meant to non-sense mediated decay (NMD).
View Article and Find Full Text PDFWhether as a cause or a symptom, RNA transcription is recurrently altered in pathologic conditions. This is also true for non-coding RNAs, with regulatory functions in a variety of processes such as differentiation, cell identity and metabolism. In line with their increasingly recognized roles in cellular pathways, RNAs are also currently evaluated as possible disease biomarkers.
View Article and Find Full Text PDFHuntington's disease (HD) is a devastating neurodegenerative disorder caused by an aberrant expansion of the CAG tract within the exon 1 of the gene, . HD progressively impairs motor and cognitive capabilities, leading to a total loss of autonomy and ultimate death. Currently, no cure or effective treatment is available to halt the disease.
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