Journal article
Longitudinal intronic RNA-Seq analysis of Parkinson’s disease patients reveals disease-specific nascent transcription
Experimental Biology and Medicine
2022
Abstract
Transcriptomic studies usually focus on either gene or exon-based annotations, and only limited experiments have reported changes in reads mapping to introns. The analysis of intronic reads allows the detection of nascent transcription that is not influenced by steady-state RNA levels and provides information on actively transcribed genes. Here, we describe substantial intronic transcriptional changes in Parkinson’s disease (PD) patients compared to healthy controls (CO) at two different timepoints; at the time of diagnosis (BL) and three years later (V08). We used blood RNA-Seq data from the Parkinson’s Progression Markers Initiative (PPMI) cohort and identified significantly changed transcription of intronic reads only in PD patients during this follow-up period. In CO subjects, only nine transcripts demonstrated differentially expressed introns between visits. However, in PD patients, 4873 transcripts had differentially expressed introns at visit V08 compared to BL, many of them in genes previously associated with neurodegenerative diseases, such as LRRK2, C9orf72, LGALS3, KANSL1AS1, and ALS2. In addition, at the time of diagnosis (BL visit), we identified 836 transcripts (e.g. SNCA, DNAJC19, PRRG4) and at visit V08, 2184 transcripts (e.g. PINK1, GBA, ALS2, PLEKHM1) with differential intronic expression specific to PD patients. In contrast, reads mapping to exonic regions demonstrated little variation indicating highly specific changes only in intronic transcription. Our study demonstrated that PD is characterized by substantial changes in the nascent transcription, and description of these changes could help to understand the molecular pathology underpinning this disease.
Details
- Title
- Longitudinal intronic RNA-Seq analysis of Parkinson’s disease patients reveals disease-specific nascent transcription
- Authors/Creators
- S. Kõks (Author/Creator)A.L. Pfaff (Author/Creator)V. J. Bubb (Author/Creator)J.P. Quinn (Author/Creator)
- Publication Details
- Experimental Biology and Medicine
- Publisher
- SAGE Publications
- Identifiers
- 991005543178807891
- Copyright
- © 2022 by The Society for Experimental Biology and Medicine
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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Source: InCites
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.52 Neurodegenerative Diseases
- 1.52.67 Parkinson's Disease
- Web Of Science research areas
- Medicine, Research & Experimental
- ESI research areas
- Clinical Medicine