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Systemic effects of the long noncoding RNA COSMOC in autism spectrum disorders

ABSTRACT: Autism Spectrum Disorders are complex neurodevelopmental disorders often attributed to specific mutated genes that collectively affect less than 10% of autists. We recently identified MOCOS, a molybdenum cofactor sulfurase-coding gene that was downregulated in stem cells of most autists of a cohort, disturbing redox homeostasis and synaptogenesis. We now report that, upstream of MOCOS, a divergent transcription generates an antisense long noncoding RNA called COSMOC. Remarkably, COSMOC expression is very low in all patients of this cohort. Knockdown studies indicates that loss of COSMOC reduces MOCOS expression, destabilizes lipid metabolism and affects energy metabolism of stem cells. Moreover, COSMOC deficiency is associated with defective neuronal maturation through the splicing regulator PTBP2 and the postsynaptic scaffold protein PSD95 involved in synaptic transmission. This dysregulation of COSMOC/MOCOS bidirectional unit might explain the origin of the disease for most autists

ORGANISM(S): Homo sapiens

PROVIDER: GSE122434 | GEO | 2019/10/01

REPOSITORIES: GEO

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