Supplementary Material for: Transcriptional Gene Silencing of the Autism-Associated Long Noncoding RNA MSNP1AS in Human Neural Progenitor Cells

The long noncoding RNA MSNP1AS (moesin pseudogene 1,
antisense) is a functional element that was previously associated with
autism spectrum disorder (ASD) with genome-wide significance. Expression
of MSNP1AS was increased 12-fold in the cerebral cortex of
individuals with ASD and 22-fold in individuals with a genome-wide
significantly associated ASD genetic marker on chromosome 5p14.1.
Overexpression of MSNP1AS in human neuronal cells caused
decreased expression of moesin protein, which is involved in neuronal
process stability. In this study, we hypothesize that MSNP1AS
knockdown impacts global transcriptome levels. We transfected the human
neural progenitor cell line SK- N-SH with constructs that caused a 50%
suppression of MSNP1AS expression. After 24 h, cells were
harvested for total RNA isolation. Strand-specific RNA sequencing
analysis indicated altered expression of 1,352 genes, including altered
expression of 318 genes following correction for multiple comparisons.
Expression of the OAS2 gene was increased >150-fold, a result
that was validated by quantitative PCR. Gene ontology analysis of the
318 genes with altered expression following correction for multiple
comparisons indicated that upregulated genes were significantly enriched
for genes involved in immune response, and downregulated genes were
significantly enriched for genes involved in chromatin remodeling. These
data indicate multiple transcriptional and translational functions of MSNP1AS
that impact ASD-relevant biological processes. Chromatin remodeling and
immune response are biological processes implicated by genes with rare
mutations associated with ASD. Our data suggest that the functional
elements implicated by association of common genetic variants impact the
same biological processes, suggesting a possible shared common
molecular pathway of ASD.