Journal article
Locus specific reduction of L1 expression in the cortices of individuals with amyotrophic lateral sclerosis
Molecular Brain, Vol.15(1), Art. 25
2022
Abstract
The activation and dysregulation of retrotransposons has been identified in the CNS of individuals with the fatal neurodegenerative disorder Amyotrophic lateral sclerosis (ALS). This includes elements from multiple different families and subfamilies of retrotransposons, however there is limited knowledge of the specific loci from which this expression occurs in ALS. The long interspersed element-1 (L1) is the only autonomous retrotransposon in the human genome and members of this family of elements maintain the ability to mobilise. Despite L1s contributing to 17% of the human genome only 80–100 L1s encode the required proteins for mobilisation and are retrotransposition competent. Identifying the specific loci from which L1 expression occurs will inform on the potential functional consequences of their expression, such as the potential for somatic retrotransposition or DNA damage caused by the endonuclease activity of the ORF2 protein of the L1. Here we characterised L1 loci expression using the L1EM tool (https://github.com/FenyoLab/L1EM) in RNA sequencing data from 518 samples across four tissues (motor cortex, frontal cortex, cerebellum and cervical spinal cord) in the Target ALS cohort obtained from the New York Genome Center. There was a significant reduction in total intact L1 expression (those that encode functional proteins) in two brain regions of individuals with ALS compared to controls and clustering of the ALS brain regions occurred based on their intact L1 expression profile. Although overall the levels of L1 expression were reduced in ALS/ALS with other neurological disorder (ND) there were individuals in which L1s were expressed at much higher levels than the rest of the ALS/ALSND cohort. Expressed L1 loci were more frequently located in introns compared to those not expressed and the level of L1 expression positively correlated with the expression of the gene in which it was located. Significant differences were observed in the expression profiles of L1s in ALS and specific features of these elements, such as location in the genome and whether or not they are intact, were significantly associated with those that were expressed in the cohort.
Details
- Title
- Locus specific reduction of L1 expression in the cortices of individuals with amyotrophic lateral sclerosis
- Authors/Creators
- A.L. Pfaff (Author/Creator) - Murdoch UniversityV.J. Bubb (Author/Creator) - University of LiverpoolJ.P. Quinn (Author/Creator) - University of LiverpoolS. Kõks (Author/Creator) - Murdoch University
- Publication Details
- Molecular Brain, Vol.15(1), Art. 25
- Publisher
- BioMed Central Ltd as part of Springer Nature
- Identifiers
- 991005545059507891
- Copyright
- © 2022 The Authors.
- Murdoch Affiliation
- Centre for Molecular Medicine and Innovative Therapeutics
- Language
- English
- Resource Type
- Journal article
UN Sustainable Development Goals (SDGs)
This output has contributed to the advancement of the following goals:
Source: InCites
Metrics
26 File views/ downloads
57 Record Views
InCites Highlights
These are selected metrics from InCites Benchmarking & Analytics tool, related to this output
- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.54 Molecular & Cell Biology - Genetics
- 1.54.1122 Transposable Elements
- Web Of Science research areas
- Neurosciences
- ESI research areas
- Neuroscience & Behavior