The novel lncRNA <i>lnc-NR2F1</i> is pro-neurogenic and mutated in human neurodevelopmental disorders.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30628890.
- Also identified by DOI 10.7554/eLife.41770 and PMC identifier 6380841.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 <i>lnc-NR2F1</i>. We further show that <i>lnc-NR2F1</i> 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.
Medical subject headings
- Autism Spectrum Disorder
- Cell Differentiation
- Mutation
- Neurodevelopmental Disorders
- Neurons
- RNA, Long Noncoding