Circular RNA is a single-stranded closed-loop structure, especially altimeter appears in the nervous system. Zhuang's research team used big data analysis to find abnormal expression of circular RNA in the cerebral cortex of autistic patients and predicted its regulatory path. Combined with molecular biology experiments, it is confirmed that circular RNA absorbs specific microribonucleic acids (mirnas) like a sponge, which makes it lose or reduce its ability to regulate downstream autism risk genes. The relationship between circular RNA, microRNA and the regulatory network of genes downstream of autism brain has not been systematically discussed in the past.
However, Academia Sinica said today that Zhuang, a researcher at the Genome Research Center, used big data analysis to find abnormally expressed circular RNA in the cerebral cortex of autistic patients and predict its regulatory path. Combined with molecular biology experiments, it is confirmed that circular RNA absorbs specific microRNA RNA (mirna) like a sponge, which makes it lose or reduce its ability to regulate downstream autism risk genes.
To detect the abnormality of circular RNA in cerebral cortex of 60 patients with autism. (Source: Academia Sinica)
Detection of 60 kinds of cyclic RNA abnormalities in cerebral cortex of autistic patients
Academia Sinica said that the team of Big Data Analysis and Neuroscience Laboratory led by Zhuang designed a big data analysis process through the previously developed circular RNA detection software (NCLscan), and found 60 circular RNA with abnormal expression in the cerebral cortex of autistic patients from more than 200 RNA-seq data samples. Statistical model analysis shows that these 60 circular RNAs can effectively distinguish autistic and non-autistic samples, so it can be judged that these circular RNAs should be related to the occurrence of autism. Academia Sinica said that the team further predicted the downstream regulatory pathways of these circular RNA and constructed an interaction regulatory network among 8 170 circular RNA, microRNA and messenger RNA. Then through gene enrichment analysis, it is found that the downstream target genes regulated by these networks are obviously concentrated in the known autism risk genes.
Circular RNA regulatory network. (Source: Academia Sinica)
The circular RNA regulatory network is highly correlated with autism risk genes.
The team of Big Data Analysis and Neuroscience Laboratory led by Zhuang designed the big data analysis process through the previously developed circular RNA detection software (NCLscan). From the RNA-seq data of more than 200 samples, 60 circular RNA with abnormal expression in the cerebral cortex of autistic patients were found. Statistical model analysis shows that these 60 circular RNAs can effectively distinguish autistic and non-autistic samples, so it can be judged that these circular RNAs should be related to the occurrence of autism.
To this end, the team further predicted the downstream regulatory pathways of these circular RNA, and constructed 8 170 interaction regulatory networks among circular RNA, microRNA and messenger RNA(mRNA). Then through gene enrichment analysis, it is found that the downstream target genes regulated by these networks are obviously concentrated in the known autism risk genes.
Zhuang said that this study not only designed a big data analysis process to construct the regulatory network relationship of circular RNA, but also verified it with meristem experiments. The team chose a circular RNA (named circARID 1A), and its expression in the brains of autistic patients increased significantly. The experiment of human nerve cells shows that circARID 1A can indeed regulate MicroRNA (Mir-204-3P).
Experiments on human nerve-related cells have proved that circARID 1A can indeed affect autism risk genes by regulating miR-204-3p.
Zhuang explained that this study not only designed a big data analysis process to construct the regulatory network relationship of circular RNA, but also verified it with meristem experiments. The research team chose a circular RNA (named circARID 1A), and its expression in the brains of autistic patients increased significantly. After verification in human nerve cell experiments, it is found that circARID 1A can really affect the expression of several downstream autism risk genes by regulating MicroRNA (Mir-204-3P).
Experiments on human nerve-related cells prove that circARID 1A can really affect the gene expression of autism risk genes by regulating miR-204-3p. (Source: Academia Sinica)