The novel lncRNA lnc-NR2F1 is pro-neurogenic and mutated in human neurodevelopmental disorders
Year: 2019
Type: article
Abstract: Long noncoding RNAs (lncRNAs) have been shown to act as important cell biological regulators including cell fate decisions but are often ignored in human genetics. Combining differential lncRNA expression during neuronal lineage induction with copy number variation morbidity maps of a cohort of children with autism spectrum disorder/intellectual disability versus healthy controls revealed focal genomic mutations affecting several lncRNA candidate loci. Here we find that a t(5:12) chromosomal translocation in a family manifesting neurodevelopmental symptoms disrupts specifically lnc-NR2F1 . We further show that lnc-NR2F1 is an evolutionarily conserved lncRNA functionally enhances induced neuronal cell maturation and directly occupies and regulates transcription of neuronal genes including autism-associated genes. Thus, integrating human genetics and functional testing in neuronal lineage induction is a promising approach for discovering candidate lncRNAs involved in neurodevelopmental diseases.
Source: eLife
DOI: 10.7554/elife.41770
Authors: Cheen Euong Ang, Qing Ma, Orly L Wapinski, ShengHua Fan, Ryan A Flynn, Qian Yi Lee, Bradley Coe, Masahiro Onoguchi, Victor Hipolito Olmos, Brian T Do, Lynn Dukes-Rimsky, Jin Xu, Koji Tanabe, LiangJiang Wang, Ulrich Elling, Josef M Penninger, Yang Zhao, Kun Qu, Evan E Eichler, Anand Srivastava, Marius Wernig, Howard Y Chang
Institutions: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford Medicine, Greenwood Genetic Center, Howard Hughes Medical Institute, University of Washington, Clemson University, Institute of Molecular Biotechnology, Austrian Academy of Sciences, Vienna Biocenter, University of Science and Technology of China
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Funders: National Science Foundation, Howard Hughes Medical Institute, California Institute for Regenerative Medicine, New York Stem Cell Foundation, California Institute of Regenerative Medicine, Österreichischen Akademie der Wissenschaften, Oesterreichische Nationalbank, National Institutes of Health, National Human Genome Research Institute, NIH Office of the Director, National Institute of Neurological Disorders and Stroke, Eunice Kennedy Shriver National Institute of Child Health and Human Development
OpenAlex ID: W2949983105