Spinocerebellar Ataxia type 1 (SCA-1) disease is caused by a CAG repeat that encodes a polyglutamine tract in Ataxin-1. Previous studies demonstrate a gain-of-function mechanism underlies this disease. The glutamine expansion alters its interactions with capicua and RBM17, regulators of RNA transcription and splicing, respectively. Successful RNA-seq projects have identified significant changes in RNA transcription and splicing between healthy and diseased mice. Recently, these researchers have demonstrated the ability to deliver an artificial oligonucleotide that knocks down Ataxin-1 RNA levels concomitantly reducing protein levels, significantly reducing the disease phenotype. This information is used to continue the researchers' search for influenced pathways and to identify transcriptional regulatory sequences.
Over the next year new genetic mouse models will be sent for RNA-seq and need to be analyzed and compared to the existing datasets. This will continue to refine the group's understanding of SCA-1. Specifically, they have created two mouse models that prevent nuclear localization of Atxn1, a transciption protein. This localization change should influence RNA expression patterns. The project uses MSI resources for data analysis and storage. Members of MSI's Research Informatics Solutions group provide bioinformatics expertise.
This group's research was featured on the MSI website in December 2020: Spinocerebellar Ataxia.