A Primate lncRNA Mediates Notch Signaling during Neuronal Development by Sequestering miRNA.
Long non-coding RNAs (lncRNAs) are a diverse and poorly conserved category of transcripts that have expanded greatly in primates, particularly in the brain. We identified an lncRNA, which has acquired 16 microRNA response elements for miR-143-3p in the Catarrhini branch of primates. This lncRNA, termed LncND (neurodevelopment), is expressed in neural progenitor cells and then declines in neurons. Binding and release of miR-143-3p by LncND control the expression of Notch receptors. LncND expression is enriched in radial glia cells (RGCs) in the ventricular and subventricular zones of developing human brain. Downregulation in neuroblastoma cells reduced cell proliferation and induced neuronal differentiation, an effect phenocopied by miR-143-3p overexpression. Gain of function of LncND in developing mouse cortex led to an expansion of PAX6+ RGCs. These findings support a role for LncND in miRNA-mediated regulation of Notch signaling within the neural progenitor pool in primates that may have contributed to the expansion of cerebral cortex.
Neuroscience Research Institute and Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
Neha
N
Rani
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 94158, USA.
Tomasz J
TJ
Nowakowski
Neuroscience Research Institute and Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
Hongjun
H
Zhou
Neuroscience Research Institute and Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
Sirie E
SE
Godshalk
Neuroscience Research Institute and Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
Véronique
V
Lisi
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 94158, USA.
Arnold R
AR
Kriegstein
Neuroscience Research Institute and Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA. Electronic address: kosik@lifesci.ucsb.edu.
Kenneth S
KS
Kosik
D000818:Animals; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism; D002552:Cerebral Ventricles / Q000378:metabolism; D063928:Ependymoglial Cells / Q000378:metabolism; D006801:Humans; D020547:Lateral Ventricles / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics*; D000071841:PAX6 Transcription Factor / Q000378:metabolism; D011323:Primates / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics*
D035683:MicroRNAs; C532884:MIRN143 microRNA, mouse; D000071841:PAX6 Transcription Factor; D062085:RNA, Long Noncoding; D051880:Receptors, Notch