The Autism-Associated Long Noncoding RNA MSNP1AS Regulates a Network of Genes Involved in Neuronal Process Stability

Background: From genome-wide association studies (GWAS), a novel gene was discovered that has a highly significant association with autism spectrum disorder (ASD). The gene is a long non-coding RNA (lncRNA) designated MSNP1AS (moesin pseudogene 1, antisense). Expression of MSNP1AS was increased in the cerebral cortex of individuals with ASD and individuals with the ASD-associated genetic marker. Overexpression of MSNP1AS in human neuronal cells caused decreased expression of moesin (MSN) mRNA and moesin MSN protein, which is involved in neuronal process stability and immune response. These data indicate one aspect of the potential contribution of increased MSNP1ASexpression in ASD. However, there are likely to be additional transcriptomic impacts of this lncRNA.

Objectives: To examine the transcriptomic impacts of the lncRNA, MSNP1AS.

Methods: To determine the effects of altered MSNP1AS expression on the neuronal transcriptome, we transfected human neuronal progenitor cells with constructs that overexpressed MSNP1AS or transcriptionally silenced MSNP1AS. 

Results: RNA-Seq analysis indicated altered expression of multiple genes that contribute to altered neuronal process stability and immune response, including MSN. 

Conclusions: Our data indicate several genes that are impacted by MSNP1AS dysregulation more significantly than MSN, suggesting a network of genes that contribute to ASD risk. Ongoing experiments seek to define the role of the MSNP1AS gene network in neuronal process stability.