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The Long Noncoding RNA Pnky Regulates Neuronal Differentiation of Embryonic and Postnatal Neural Stem Cells
Open accessAbstract
While thousands of long noncoding RNAs (lncRNAs) have been identified, few lncRNAs that control neural stem cell (NSC) behavior are known. Here, we identify Pinky (Pnky) as a neural-specific lncRNA that regulates neurogenesis from NSCs in the embryonic and postnatal brain. In postnatal NSCs, Pnky knockdown potentiates neuronal lineage commitment and expands the transit-amplifying cell population, increasing neuron production several-fold. Pnky is evolutionarily conserved and expressed in NSCs of the developing human brain. In the embryonic mouse cortex, Pnky knockdown increases neuronal differentiation and depletes the NSC population. Pnky interacts with the splicing regulator PTBP1, and PTBP1 knockdown also enhances neurogenesis. In NSCs, Pnky and PTBP1 regulate the expression and alternative splicing of a core set of transcripts that relates to the cellular phenotype. These data thus unveil Pnky as a conserved lncRNA that interacts with a key RNA processing factor and regulates neurogenesis from embryonic and postnatal NSC populations.
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“Lastly, non-coding RNA processing and RNA splicing showed lateral wall enrichment, consistent with the importance of non-coding RNAs in V-SVZ neurogenesis (Ramos et al., 2015; Figure 2C; Table S3).”
From Single-Cell Analysis of Regional Differences in Adult V-SVZ Neural Stem Cell Lineages (2019) · cites this paper as Ramos et al., 2015
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The functions and unique features of long intergenic non-coding RNA
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“Two lnc-RNAs, Six3os and Dlx1as, promote neuronal differentiation and repress astrocytic differentiation of NSCs, whereas another lnc-RNA, Pnky, inhibits NSC differentiation (Ramos et al., 2013, 2015).”
BackgroundCRISPRi-based genome-scale identification of functional long noncoding RNA loci in human cells
Liu, S. J., Horlbeck, M. A., Cho, S. W., Birk, H. S., Malatesta, M., He, D. X., Attenello, F. J., Villalta, J. E., Cho, M. Y., Chen, Y., et al. (2016) · Science · doi:10.1126/science.aah7111 · Cited by 756
The Adult Ventricular–Subventricular Zone (V-SVZ) and Olfactory Bulb (OB) Neurogenesis
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Self-citation
Metadata
- Authors
- Ramos, A. D., Andersen, R. E., Liu, S. J., Nowakowski, T. J., Hong, S. J., Gertz, C. C., Salinas, R. D., Zarabi, H., Kriegstein, A. R., & Lim, D. A.
- Affiliations
- University of California, San Francisco (US)
- San Francisco VA Medical Center (US)
- Corresponding author
- Lim, Daniel A.
- ORCID
- Venue
- Cell stem cell
- Publisher
- Elsevier BV
- Published
- 2015-04
- Volume
- 16
- Issue
- 4
- Pages
- 439-447
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC4388801
- OpenAlex
- W1981435333
- Cited by
- 359
- References
- 56
- Citations by year
- 2026: 13 · 2025: 15 · 2024: 21 · 2023: 35 · 2022: 35 · 2021: 46 · 2020: 43 · 2019: 37 · 2018: 29 · 2017: 37 · 2016: 33 · 2015: 14
- FWCI
- 15.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- U.S. Department of Veterans Affairs (I01BX000252)
- National Science Council
- National Institutes of Health (1f31ns080501-01a1, 5f30ns092319-02, 1dp2od006505-01)
- University of California, San Francisco
- National Institute of General Medical Sciences (T32GM007618)
- National Institute of Neurological Disorders and Stroke (R01NS035710, F30 NS092319, R01 NS35710, F31 NS080501, 1F31NS080501-01A1)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD007470)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- long non-coding RNA, neural stem cells, neurogenesis, neuronal differentiation, PTBP1, alternative splicing, transit amplifying cells, embryonic cortex, postnatal brain, RNA processing
- MeSH terms
- Animals, Base Sequence, Brain, Cells, Cultured, Embryo, Mammalian, Humans, Mice, Inbred C57BL, Molecular Sequence Data, Neurons, Alternative Splicing, Heterogeneous-Nuclear Ribonucleoproteins, RNA, Small Interfering, Polypyrimidine Tract-Binding Protein, Mice, Embryonic Stem Cells, Neurogenesis, Neural Stem Cells, RNA, Long Noncoding
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