Abstract
We previously identified the long noncoding RNA (lncRNA) MSNP1AS (moesin pseudogene 1, antisense) as a functional element revealed by genome wide significant association with autism spectrum disorder (ASD). MSNP1AS expression was increased in the postmortem cerebral cortex of individuals with ASD and particularly in individuals with the ASD-associated genetic markers on chromosome 5p14.1. Here, we mimicked the overexpression of MSNP1AS observed in postmortem ASD cerebral cortex in human neural progenitor cell lines to determine the impact on neurite complexity and gene expression. ReNcell CX and SK-N-SH were transfected with an overexpression vector containing full-length MSNP1AS. Neuronal complexity was determined by the number and length of neuronal processes. Gene expression was determined by strand-specific RNA sequencing. MSNP1AS overexpression decreased neurite number and neurite length in both human neural progenitor cell lines. RNA sequencing revealed changes in gene expression in proteins involved in two biological processes: protein synthesis and chromatin remodeling. These data indicate that overexpression of the ASD-associated lncRNA MSNP1AS alters the number and length of neuronal processes. The mechanisms by which MSNP1AS overexpression impacts neuronal differentiation may involve protein synthesis and chromatin structure. These same biological processes are also implicated by rare mutations associated with ASD, suggesting convergent mechanisms.
Highlights
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and repetitive behaviors with restricted interests [1,2]
Rare, de novo loss of function mutations has been associated with ASD, and many of the associated genes converge upon the biological processes of protein synthesis and chromatin structure [3,4]
MSNP1AS was discovered as the functional element revealed by an ASD genome-wide association the of long noncoding RNA (lncRNA)
Summary
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and repetitive behaviors with restricted interests [1,2]. Rare, de novo loss of function mutations has been associated with ASD, and many of the associated genes converge upon the biological processes of protein synthesis and chromatin structure [3,4]. The same rs4307059 allele was identified as a predictor or stereotyped conversation and poorer communication skills in a population-based sample of >7000 individuals [8], suggesting. Genes 2016, 7, 76 that rs4307059 may be a quantitative trait locus for social communication phenotypes. We identified a 3.9 kb long noncoding RNA (lncRNA) that is transcribed directly at the site of the chromosome
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