A noncoding RNA antisense to moesin at 5p14.1 in autism

Area of Science:

• Genetics
• Neuroscience
• Molecular Biology

Background:

• Autism spectrum disorder (ASD) is characterized by social, language, and behavioral deficits.
• While rare mutations are known, causal variants for most ASD cases remain unidentified.
• A genome-wide association study identified a significant association between ASD and SNP rs4307059 on chromosome 5p14.1.

Purpose of the Study:

• To identify and characterize a functional noncoding RNA associated with ASD risk.
• To investigate the role of this noncoding RNA in ASD pathogenesis.

Main Methods:

• Identification of a 3.9-kb noncoding RNA (MSNP1AS) transcribed antisense to MSNP1.
• Analysis of MSNP1AS expression in relation to the ASD-associated SNP rs4307059.
• Assessment of MSNP1AS interaction with MSN and its effect on moesin protein levels in cell lines.
• Quantification of MSNP1AS and moesin expression in postmortem ASD brain tissue.

Main Results:

• A novel noncoding RNA, MSNP1AS, was identified in the 5p14.1 region associated with ASD.
• Individuals with the ASD-associated rs4307059 T allele exhibited increased MSNP1AS expression.
• MSNP1AS was highly overexpressed (12.7-fold) in the cerebral cortex of individuals with ASD.
• MSNP1AS demonstrated binding to MSN and could regulate moesin protein levels.

Conclusions:

• MSNP1AS is a biologically functional noncoding RNA potentially contributing to ASD risk.
• The dysregulation of MSNP1AS and its interaction with moesin may play a role in ASD pathophysiology.
• This finding highlights a novel molecular mechanism implicated in autism spectrum disorder.