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Vol 24, No. 06, June 2020   |   Issue PDF view/purchase
Autism-Associated Circular RNA Regulatory Networks
Researchers from the Genomics Research Center, Academia Sinica, provide a framework for assessing the involvement of circular RNA in autism spectrum disorder (ASD).

Autism spectrum disorder (ASD) is a pervasive neurodevelopmental and heritable complex disorder characterized by limited social communication, restricted and ritualized interests, and repetitive behaviour. In Taiwan, ASD afflicts more than 15,400 people (the 2019鈥檚 report from Ministry of Health and Welfare, Taiwan); and its prevalence is increasing. Hundreds of genes affected by a variety of genomic variants have been reported to be associated with the aetiology of ASD.

Studies in the past have provided biological insights to ASD but due to the high heterogeneity of the disease each factor accounts for a very low percentage of the general ASD population. Additionally, environmental and gene-environment interactions have largely been demonstrated to be associated with the development of ASD.

Circular RNAs (circRNAs) are a class of long non-coding RNAs produced by pre-mRNA back-splicing, which generates a structure of covalently closed loop of single-strand, non-polyadenylated circular molecules. The stability of circRNAs make them possible viable therapeutic targets for neurological disorders. Many studies have also shown that circRNAs play an important role in the development of the nervous system.

In this study, the researchers utilized small RNA-seq data and RNA-seq data, both of which were downloaded from the Synapse database, to investigate genome-wide circRNA expression profiling in post-mortem brains from ASD patients and non-ASD controls. The team also identified circRNA and demonstrated its expression profiles were very similar between two types of cortex regions but were quite distinct from that of cerebellum.

Through their analysis the scientists found 60 DE-circRNAs, in which 22 were upregulated and 38 were downregulated in ASD cortex. They also discovered that three modules were significantly correlated with ASD status. Further to that they identified potentially ASD-associated circRNA-miRNA-mRNA regulatory axes.

In addition, the team validated the identified circRNA-miRNA-mRNA regulatory interactions and confirmed the involvement of some ASD risk genes which were regulated by circARIDIA.

Taken together, the study has provided a framework for assessing the functional involvement of circRNA in ASD and the corresponding ASD-associated circRNA-miRNA-mRNA regulatory axes.

The research group has provided a rich set of ASD-associated circRNA candidates and the corresponding circRNA-miRNA-mRNA axes, particularly those involving ASD risk genes, for further investigation in ASD pathophysiology. This is to their knowledge the first systems-level view of landscape of circRNA regulatory networks in ASD cortex samples. The proposed framework offers further analysis of circRNAs in other human complex diseases such as Alzheimer鈥檚 disease, Parkinson's disease, and schizophrenia.

The study was published in Genome Research in March 2020.


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