The novel lncRNA lnc-NR2F1 is proneurogenic 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 SrivastavaMarius Wernig*, Howard Y. Chang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

47 Citations (Scopus)


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.

Original languageEnglish
Article numbere41770
Publication statusPublished - 2019
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)


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