Non-Coding RNAs in Autism

Background:   The human genome mostly consists of DNA that does not encode for protein. Although originally thought to represent evolutionary ‘junk,’ it has been shown that much of the non-coding DNA in the human genome is actively transcribed to RNA in a highly regulated, tissue-specific manner. 

Objectives:   Following this insight, non-coding RNAs (ncRNAs) were demonstrated to be fundamental to many intracellular processes, such as targeting transcription factors to their binding sites, initiating chromatin remodeling, blocking transcription or translation of other genes both in cis and trans, and a variety of other functions that are still being uncovered. Perhaps not surprisingly, studies quickly followed showing that disruption of ncRNA biogenesis can lead to molecular and cellular defects. 

Methods:   Recently, ncRNAs have been demonstrated to be abnormal in the brains of patients with common neurodevelopmental disorders and their animal models, such as autism, schizophrenia, and bipolar disorder. These diseases were previously known to have a significant hereditary component, but their genomic etiology is complex and has remained poorly understood. 

Results:   Emerging research into underlying ncRNA problems in these disorders has the potential to reconcile their known heritability with their genomic and phenotypic heterogeneity, and hopefully unveil novel genomic pathologic mechanisms that can ultimately lead to new molecular therapeutics. In this presentation, we will present a broad overview of previous findings from our laboratory and others that have implicated long non-coding RNAs and short non-coding RNAs (such as microRNAs) in idiopathic autism. 

Conclusions:  

We will also present new work investigating non-coding RNAs expressed from the mitochondrial genome that appear altered in autistic brain.

Note: MNZ is an ‘early career investigator’ as defined by IMFAR