title: The long noncoding RNA Pnky regulates neuronal differentiation of embryonic and postnatal neural stem cells.
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.
authors: Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.|Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA.|Medical Scientist Training Program, Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA.
authors: Alexander D
authors: AD
authors: Ramos
authors: Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.|Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA.|Developmental and Stem Cell Biology Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA.
authors: Rebecca E
authors: RE
authors: Andersen
authors: Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.|Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA.|Medical Scientist Training Program, Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA.
authors: Siyuan John
authors: SJ
authors: Liu
authors: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA.|Department of Neurology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors: Tomasz Jan
authors: TJ
authors: Nowakowski
authors: Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.|Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA.|CIRM-Masters Program, San Francisco State University, San Francisco, CA 94132, USA.
authors: Sung Jun
authors: SJ
authors: Hong
authors: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA.|Department of Neurology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors: Caitlyn
authors: C
authors: Gertz
authors: Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.|Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA.
authors: Ryan D
authors: RD
authors: Salinas
authors: Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.|Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA.
authors: Hosniya
authors: H
authors: Zarabi
authors: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA.|Department of Neurology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors: Arnold R
authors: AR
authors: Kriegstein
authors: Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.|Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA.|San Francisco Veterans Affairs Medical Center, San Francisco, CA 94121, USA.
authors: Daniel A
authors: DA
authors: Lim
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D053595:Embryonic Stem Cells / Q000502:physiology*; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D058953:Neural Stem Cells / Q000502:physiology*; D055495:Neurogenesis / Q000235:genetics; D009474:Neurons / Q000502:physiology*; D038941:Polypyrimidine Tract-Binding Protein / Q000235:genetics / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D034441:Heterogeneous-Nuclear Ribonucleoproteins; C450006:PTBP1 protein, human; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; D038941:Polypyrimidine Tract-Binding Protein