Alternative splicing generates a Ribosomal Protein S24 isoform induced by neuroinflammation and neurodegeneration Article Swipe
Srivathsa S. Magadi
,
Maria Jonson
,
Joseph Agi Maqdissi
,
Lech Kaczmarczyk
,
J Zijlstra
,
Matthew Perkins
,
Gesine Paul
,
Martin Hallbeck
,
Martin Ingelsson
,
Joel C. Watts
,
Nicole Reichenbach
,
Gabor C. Petzold
,
Pablo Botella Lucena
,
Michael T. Heneka
,
Walker S. Jackson
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.03.28.645676
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.03.28.645676
Neuroinflammation, particularly that involving reactive microglia, the brain’s resident immune cells, is implicated in the pathogenesis of major neurodegenerative diseases. However, early markers of this process are in high demand. Multiple studies have reported changes in ribosomal protein (RP) expression during neurodegeneration, but the significance of these changes remains unclear. Ribosomes are evolutionarily conserved protein synthesizing machines, and although commonly viewed as invariant, accumulating evidence suggest functional ribosome specialization through variation in their protein composition. By analyzing cell type-specific translating mRNAs from mouse brains, we identify distinct RP expression patterns between neurons, astrocytes, and microglia, including neuron-specific RPs, Rpl13a and Rps10 . We also observed complex expression relationships between RP paralogs and their canonical counterparts, suggesting regulated mechanisms for generating heterogeneous ribosomes. Analysis across brain regions revealed that Rplp0 and Rpl13a , commonly used normalization references, show heterogeneous expression, raising important methodological considerations for gene expression studies. Importantly, we show that Rps24 , an essential ribosome component that undergoes alternative splicing to produce protein variants with different C-termini, exhibits striking cell type-specific isoform expression in brain. The Rps24c isoform is predominantly expressed in microglia and is increased by neuroinflammation caused by aging, neurodegeneration, or inflammatory chemicals. We verify increased expression of S24-PKE, the protein variant encoded by Rps24c , in brains with Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, and relevant mouse models, using isoform-specific antibodies. These findings establish heterogeneous RP expression as a feature of brain cell types and identify Rps24c /S24-PKE as a novel marker for neuroinflammation and neurodegeneration.
Related Topics
Concepts
Neurodegeneration
Neuroinflammation
Gene isoform
RNA splicing
Alternative splicing
Ribosomal RNA
Ribosomal protein
Neuroscience
Biology
Computational biology
Cell biology
Genetics
Medicine
Disease
Gene
RNA
Immunology
Internal medicine
Ribosome
Inflammation
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2025.03.28.645676
- OA Status
- green
- References
- 77
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4409087501
All OpenAlex metadata
Raw OpenAlex JSON
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https://openalex.org/W4409087501Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2025.03.28.645676Digital Object Identifier
- Title
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Alternative splicing generates a Ribosomal Protein S24 isoform induced by neuroinflammation and neurodegenerationWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
- Publication date
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2025-04-02Full publication date if available
- Authors
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Srivathsa S. Magadi, Maria Jonson, Joseph Agi Maqdissi, Lech Kaczmarczyk, J Zijlstra, Matthew Perkins, Gesine Paul, Martin Hallbeck, Martin Ingelsson, Joel C. Watts, Nicole Reichenbach, Gabor C. Petzold, Pablo Botella Lucena, Michael T. Heneka, Walker S. JacksonList of authors in order
- Landing page
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https://doi.org/10.1101/2025.03.28.645676Publisher landing page
- Open access
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YesWhether a free full text is available
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greenOpen access status per OpenAlex
- OA URL
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https://doi.org/10.1101/2025.03.28.645676Direct OA link when available
- Concepts
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Neurodegeneration, Neuroinflammation, Gene isoform, RNA splicing, Alternative splicing, Ribosomal RNA, Ribosomal protein, Neuroscience, Biology, Computational biology, Cell biology, Genetics, Medicine, Disease, Gene, RNA, Immunology, Internal medicine, Ribosome, InflammationTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
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77Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| primary_location.landing_page_url | https://doi.org/10.1101/2025.03.28.645676 |
| publication_date | 2025-04-02 |
| publication_year | 2025 |
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