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.
journal_name
Elifejournal_title
eLifeauthors
Ang CE,Ma Q,Wapinski OL,Fan S,Flynn RA,Lee QY,Coe B,Onoguchi M,Olmos VH,Do BT,Dukes-Rimsky L,Xu J,Tanabe K,Wang L,Elling U,Penninger JM,Zhao Y,Qu K,Eichler EE,Srivastava A,Wernig M,Chang HYdoi
10.7554/eLife.41770subject
Has Abstractpub_date
2019-01-10 00:00:00issn
2050-084Xpii
41770journal_volume
8pub_type
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