Intronic miR-26b controls neuronal differentiation by repressing its host transcript,ctdsp2
Open accessAbstract
Differentiation of neural stem cells (NSCs) to neurons requires the activation of genes controlled by the repressor element 1 (RE1) silencing transcription factor (REST)/neuron-restrictive silencer factor (NRSF) protein complex. Important components of REST/NRSF are phosphatases (termed RNA polymerase II C-terminal domain small phosphatases [CTDSPs]) that inhibit RNA polymerase II and suppress neuronal gene expression in NSCs. Activation of genes controlled by CTDSPs is required for neurogenesis, but how this is achieved is not fully understood. Here we show that ctdsp2 is a target of miR-26b, a microRNA that is encoded in an intron of the ctdsp2 primary transcript. This intrinsic negative feedback loop is inactive in NSCs because miR-26b biogenesis is inhibited at the precursor level. Generation of mature miR-26b is activated during neurogenesis, where it suppresses Ctdsp2 protein expression and is required for neuronal cell differentiation in vivo.
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- Authors
- Dill, H., Linder, B., Fehr, A., & Fischer, U.
- Affiliations
- University of Würzburg (DE)
- University of Zurich (CH)
- Corresponding author
- Fischer, Utz
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2012-01-01
- Volume
- 26
- Issue
- 1
- Pages
- 25-30
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC3258962
- OpenAlex
- W1978402873
- Cited by
- 125
- References
- 35
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 6 · 2022: 1 · 2021: 7 · 2020: 10 · 2019: 5 · 2018: 13 · 2017: 12 · 2016: 16 · 2015: 20 · 2014: 9 · 2013: 11 · 2012: 7
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- miR-26b, microRNA host gene, intronic microRNA, REST/NRSF, neural stem cell differentiation, neuronal differentiation, neurogenesis, negative feedback loop, microRNA biogenesis, RNA polymerase II C-terminal domain
- MeSH terms
- Animals, Cell Differentiation, Embryo, Nonmammalian, Introns, Neurons, Phosphoprotein Phosphatases, Zebrafish, Down-Regulation, Gene Expression Regulation, Developmental, Gene Expression Profiling, Zebrafish Proteins, MicroRNAs, Cell Line, Tumor, Mice, Neurogenesis
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