Publications by authors named "Jharrayne I McKnight"
Huntington's disease (HD) is caused by a CAG repeat expansion in the HTT gene, leading to altered gene expression. However, the mechanisms leading to disrupted RNA processing in HD remain unclear. Here we identify TDP-43 and the N6-methyladenosine (m6A) writer protein METTL3 to be upstream regulators of exon skipping in multiple HD systems.
View Article and Find Full Text PDFArticle Synopsis
- Huntington's disease (HD) is linked to a CAG repeat expansion in the huntingtin gene, leading to disrupted RNA processing, though the exact mechanisms were previously unclear.
- Analysis of the huntingtin protein interactions revealed that RNA-binding proteins (RBPs), particularly TDP-43 and the m6A writer METTL3, play key roles in increased exon skipping observed in HD.
- Decreased nuclear localization of TDP-43 and reduced m6A RNA modification on specific RNAs in the HD model suggest a novel mechanism of altered gene expression contributing to HD pathology.