Alternative Splicing Coupled Nonsense-Mediated Decay Generates Neuronal Cell Type-Specific Expression of SLM Proteins
Open accessAbstract
The unique physiological and morphological properties of neuronal populations are crucial for the appropriate functioning of neuronal circuits. Alternative splicing represents an attractive mechanism for generating cell type-specific molecular repertoires that steer neuronal development and function. However, the mechanisms that link neuronal identity to alternative splicing programs are poorly understood. We report that cell type-specific, mutually exclusive expression of two alternative splicing regulators, SLM1 and SLM2, in the mouse hippocampus is achieved by a cross-repression mechanism. Deletion of SLM2 in vivo modifies alternative splicing of its paralog Slm1 and stabilizes its mRNA, resulting in expression of SLM1 in previously SLM2-expressing cells. Despite this ectopic upregulation of SLM1, loss of SLM2 severely disrupts the alternative splicing regulation of Nrxn1,Nrxn2, and Nrxn3, highlighting that the two SLM paralogs have partially divergent functions. Our study uncovers a hierarchical, SLM2-dependent mechanism for establishing cell type-specific expression of neuronal splicing regulators in vivo.
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Slm1 and Slm2 single-null mice are viable with no apparent behavioural or anatomical defects.
“Slm1 and Slm2 single-null mice are viable with no apparent behavioural or anatomical defects84,87,98.”
From The neurogenetics of alternative splicing (2016) · cites this paper as [87]
SLM2 depletion shifts the splicing of Slm1 away from an NMD-targeted isoform and towards a productive transcript.
“Specifically, SLM2 depletion shifts the splicing of Slm1 away from an NMD-targeted isoform and towards a productive transcript87.”
From The neurogenetics of alternative splicing (2016) · cites this paper as [87]
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References 28 · Cited by 40
- Authors
- Traunmüller, L., Bornmann, C., & Scheiffele, P.
- Affiliations
- University of Basel (CH)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2014-12-10
- Volume
- 34
- Issue
- 50
- Pages
- 16755-16761
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6608507
- OpenAlex
- W2052710304
- Cited by
- 40
- References
- 28
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 1 · 2022: 6 · 2021: 3 · 2020: 4 · 2019: 3 · 2018: 5 · 2017: 2 · 2016: 8 · 2015: 1 · 2013: 1
- FWCI
- 1.50
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- edoc (University of Basel) (acceptedVersion)
- edoc (University of Basel)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Innovative Medicines Initiative
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- alternative splicing, nonsense-mediated mRNA decay, splicing regulators, mRNA stability, NRXN1, NRXN3, hippocampus, neuronal identity, paralog divergence
- MeSH terms
- Animals, Female, Gene Expression Regulation, Hippocampus, Humans, Male, Neurons, RNA-Binding Proteins, Alternative Splicing, Mice, Knockout, Mice, Mice, 129 Strain, HEK293 Cells, Nonsense Mediated mRNA Decay
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