Impact of the Autism-Associated Long Noncoding RNA MSNP1AS on Neuronal Architecture and Gene Expression in Human Neural Progenitor Cells

Abstract

We previously identified the long noncoding RNA (lncRNA) <i>MSNP1AS</i> (moesin pseudogene 1, antisense) as a functional element revealed by genome wide significant association with autism spectrum disorder (ASD). <i>MSNP1AS</i> 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 <i>MSNP1AS</i> 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 <i>MSNP1AS</i>. Neuronal complexity was determined by the number and length of neuronal processes. Gene expression was determined by strand-specific RNA sequencing. <i>MSNP1AS</i> 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 <i>MSNP1AS</i> alters the number and length of neuronal processes. The mechanisms by which <i>MSNP1AS</i> 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.