The long noncoding RNA Pnky regulates neuronal differentiation of embryonic and postnatal neural stem cells

Alexander D Ramos; Rebecca E Andersen; Siyuan John Liu; Tomasz Jan Nowakowski; Sung Jun Hong; Caitlyn Gertz; Ryan D Salinas; Hosniya Zarabi; Arnold R Kriegstein; Daniel A Lim

doi:10.1016/j.stem.2015.02.007

The long noncoding RNA Pnky regulates neuronal differentiation of embryonic and postnatal neural stem cells

Cell Stem Cell. 2015 Apr 2;16(4):439-447. doi: 10.1016/j.stem.2015.02.007. Epub 2015 Mar 19.

Authors

Alexander D Ramos^#^{1

2

3}, Rebecca E Andersen^#^{1

2

4}, Siyuan John Liu^{1

2

3}, Tomasz Jan Nowakowski^{2

5}, Sung Jun Hong^{1

2

6}, Caitlyn Gertz^{2

5}, Ryan D Salinas^{1

2}, Hosniya Zarabi^{1

2}, Arnold R Kriegstein^{2

5}, Daniel A Lim^{1

2

7}

Affiliations

¹ Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
² Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA.
³ Medical Scientist Training Program, Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA.
⁴ Developmental and Stem Cell Biology Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA.
⁵ Department of Neurology, University of California, San Francisco, San Francisco, CA 94143, USA.
⁶ CIRM-Masters Program, San Francisco State University, San Francisco, CA 94132, USA.
⁷ San Francisco Veterans Affairs Medical Center, San Francisco, CA 94121, USA.

^# Contributed equally.

Abstract

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Alternative Splicing / genetics
Animals
Base Sequence
Brain / metabolism*
Cells, Cultured
Embryo, Mammalian
Embryonic Stem Cells / physiology*
Heterogeneous-Nuclear Ribonucleoproteins / genetics
Heterogeneous-Nuclear Ribonucleoproteins / metabolism*
Humans
Mice
Mice, Inbred C57BL
Molecular Sequence Data
Neural Stem Cells / physiology*
Neurogenesis / genetics
Neurons / physiology*
Polypyrimidine Tract-Binding Protein / genetics
Polypyrimidine Tract-Binding Protein / metabolism*
RNA, Long Noncoding / genetics
RNA, Long Noncoding / metabolism*
RNA, Small Interfering / genetics

Substances

Heterogeneous-Nuclear Ribonucleoproteins
PTBP1 protein, human
RNA, Long Noncoding
RNA, Small Interfering
Polypyrimidine Tract-Binding Protein

Associated data

GENBANK/KP881340
GENBANK/KP881341
GEO/GSE65542

Abstract

Publication types

MeSH terms

Substances

Associated data

Grants and funding