McDonald, Jamie and Langley, Sarah  ORCID: https://orcid.org/0000-0003-4419-476X
2026.
RNA processing dysregulation in Huntington’s disease [Conference Abstract].
Journal of Neurology, Neurosurgery and Psychiatry
97
(Supp 2)
, pp. A5-A6.
10.1136/jnnp-2026-ehdn.12
|
Abstract
Background: Huntington’s Disease (HD) is a neurodegenerative disease caused by CAG repeat expansions in the Huntingtin (HTT) gene, leading to progressive striatal atrophy. Widespread dysregulated alternative splicing (AS) and incidents of alternative polyadenylation (APA) have been previously identified, but integrative analysis of multiple RNA processing levels in HD is lacking1,2. We hypothesise mutant HTT disrupts RNA processing, contributing to HD pathology. Aims: We aim to understand if RNA processing dysregulation contributes to HD pathology, across developmental stages and CAG lengths, representing different onset ages. Methods: We analysed RNA-seq data from an established human isogenic system. Embryonic stem cells (ESCs) were differentiated into neural progenitor cells (NPCs) across a range of CAG repeat lengths corresponding to control, late onset HD, and early onset HD3. Within the ESCs and NPCs, we performed a comprehensive global RNA processing events analysis–including evaluating individual AS and APA events and interrogating the putative downstream effects on transcript abundance and usage–to detect impaired RNA processing between control and expanded CAG lengths. Results: In addition to our previous AS work, we identified widespread and significant APA and transcript level dysregulation associated with CAG repeat expansion. We find a higher number of events and altered transcripts in the ESCs as compared to the NPCs. Notably, the genes with altered RNA processing are they themselves involved in RNA processing. Conclusion: We find extensive RNA processing dysregulation in HD and suggest a feedback loop between RNA processing layers. These findings support our integrative approach.
| Item Type: | Short Communication |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Schools > Biosciences |
| Publisher: | BMJ Publishing Group |
| ISSN: | 0022-3050 |
| Last Modified: | 26 Oct 2026 12:30 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/190426 |
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