eLife (Jan 2019)
The novel lncRNA lnc-NR2F1 is pro-neurogenic and mutated in human neurodevelopmental disorders
- 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
Affiliations
- Cheen Euong Ang
- ORCiD
- Department of Pathology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, United States; Department of Bioengineering, Stanford University, Stanford, United States
- Qing Ma
- ORCiD
- Center for Personal Dynamic Regulomes, Stanford University, Stanford, United States; Department of Dermatology, Stanford University, Stanford, United States; Department of Genetics, Stanford University, Stanford, United States
- Orly L Wapinski
- Center for Personal Dynamic Regulomes, Stanford University, Stanford, United States; Department of Dermatology, Stanford University, Stanford, United States; Department of Genetics, Stanford University, Stanford, United States
- ShengHua Fan
- JC Self Research Institute of Human Genetics, Greenwood Genetic Center, Greenwood, United States
- Ryan A Flynn
- Center for Personal Dynamic Regulomes, Stanford University, Stanford, United States; Department of Dermatology, Stanford University, Stanford, United States; Department of Genetics, Stanford University, Stanford, United States
- Qian Yi Lee
- ORCiD
- Department of Pathology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, United States; Department of Bioengineering, Stanford University, Stanford, United States
- Bradley Coe
- Department of Genome Sciences, Howard Hughes Medical Institute, University of Washington, Seattle, United States
- Masahiro Onoguchi
- Center for Personal Dynamic Regulomes, Stanford University, Stanford, United States; Department of Dermatology, Stanford University, Stanford, United States; Department of Genetics, Stanford University, Stanford, United States
- Victor Hipolito Olmos
- Department of Pathology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, United States
- Brian T Do
- Center for Personal Dynamic Regulomes, Stanford University, Stanford, United States
- Lynn Dukes-Rimsky
- JC Self Research Institute of Human Genetics, Greenwood Genetic Center, Greenwood, United States
- Jin Xu
- ORCiD
- Center for Personal Dynamic Regulomes, Stanford University, Stanford, United States
- Koji Tanabe
- Department of Pathology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, United States
- LiangJiang Wang
- Department of Genetics and Biochemistry, Clemson University, Clemson, United States
- Ulrich Elling
- Institute of Molecular Biotechnology of the Austrian Academy of Science (IMBA), Vienna Biocenter, Vienna, Austria
- Josef M Penninger
- ORCiD
- Institute of Molecular Biotechnology of the Austrian Academy of Science (IMBA), Vienna Biocenter, Vienna, Austria
- Yang Zhao
- Center for Personal Dynamic Regulomes, Stanford University, Stanford, United States
- Kun Qu
- Center for Personal Dynamic Regulomes, Stanford University, Stanford, United States; Institute of Molecular Biotechnology of the Austrian Academy of Science (IMBA), Vienna Biocenter, Vienna, Austria
- Evan E Eichler
- ORCiD
- Department of Genome Sciences, Howard Hughes Medical Institute, University of Washington, Seattle, United States
- Anand Srivastava
- JC Self Research Institute of Human Genetics, Greenwood Genetic Center, Greenwood, United States; Department of Genetics and Biochemistry, Clemson University, Clemson, United States
- Marius Wernig
- Department of Pathology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, United States
- Howard Y Chang
- ORCiD
- Center for Personal Dynamic Regulomes, Stanford University, Stanford, United States
- DOI
- https://doi.org/10.7554/eLife.41770
- Journal volume & issue
-
Vol. 8
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.
Keywords
