The novel lncRNA lnc-NR2F1 is proneurogenic and mutated in human neurodevelopmental disorders

被引:51
作者
Ang, Cheen Euong [1 ,2 ]
Ma, Qing [3 ,4 ,5 ]
Wapinski, Orly L. [3 ,4 ,5 ]
Fan, ShengHua [6 ]
Flynn, Ryan A. [3 ,4 ,5 ]
Lee, Qian Yi [1 ,2 ]
Coe, Bradley [7 ]
Onoguchi, Masahiro [3 ,4 ,5 ]
Olmos, Victor Hipolito [1 ]
Do, Brian T. [3 ]
Dukes-Rimsky, Lynn [6 ]
Xu, Jin [3 ]
Tanabe, Koji [1 ]
Wang, LiangJiang [8 ]
Elling, Ulrich [9 ]
Penninger, Josef M. [9 ]
Zhao, Yang [3 ]
Qu, Kun [3 ,9 ,10 ]
Eichler, Evan E. [7 ]
Srivastava, Anand [6 ,8 ]
Wernig, Marius [1 ]
Chang, Howard Y. [3 ]
机构
[1] Stanford Univ, Dept Pathol, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA
[2] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA
[3] Stanford Univ, Ctr Personal Dynam Regulomes, Stanford, CA 94305 USA
[4] Stanford Univ, Dept Dermatol, Stanford, CA 94305 USA
[5] Stanford Univ, Dept Genet, Stanford, CA 94305 USA
[6] Greenwood Genet Ctr, JC Self Res Inst Human Genet, Greenwood, SC 29646 USA
[7] Univ Washington, Howard Hughes Med Inst, Dept Genome Sci, Seattle, WA 98195 USA
[8] Clemson Univ, Dept Genet & Biochem, Clemson, SC USA
[9] Austrian Acad Sci IMBA, Vienna Bioctr, Inst Mol Biotechnol, Vienna, Austria
[10] Univ Sci & Technol China, Sch Life Sci & Med Ctr, CAS Key Lab Innate Immun & Chron Dis, Hefei, Anhui, Peoples R China
关键词
LONG NONCODING RNAS; MOUSE-BRAIN DEVELOPMENT; NEURAL STEM-CELLS; NEURONAL DIFFERENTIATION; FUNCTIONAL-NEURONS; COUP-TFI; CHROMATIN; AUTISM; FIBROBLASTS; GENES;
D O I
10.7554/eLife.41770
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页数:29
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