Identification And Analysis Of Circular RNA In Human And Mouse

CircRNA is a class of noncoding RNA molecule with closed loop structure.In recent years,the development of second-generation sequencing technology and bioinformatics progress make it possible to study circRNA on a large scale.At present,the study of circRNA is still in the initial stage of development,the function of many circRNA is unkown and the existing mechanism of circRNA biogenesis is not perfect.Here we utilize RNA-Seq data of four human cell lines and one mouse cell line,and identify circRNAs by running find_circ,CIRCexplorer and CIRI,and we integrate ChIA-PET data to explore the mechanism of circRNA biogenesis.We focus our study on GM12878 and K562 cell line.The main contents of the analysis include circRNA identification,basic feature analysis,the mechanism of circRNA biogenesis exploration,chromatin interaction network that host gene involved,and the initial analysis of circRNA function.The detailed results are as follows:In K562,GM12878,HeLa,h ESC and mESC cell line,we identified 3275,2682,1501,1819,708 circRNAs derived from 1871,1687,1070,1264,571 host genes respectively,these highly reliable circRNAs are used for further analysis.CircRNAs tend to use the middle exon of transcripts to cyclize and have longer flanking introns,and there are many Alu elements and binding sites of SRSF3 protein in flank intron.Its expression is cell specific,and the more conserved circular RNA between cell lines,the higher expression level.A few circRNAs originate from the first and last exon of transcripts.By using ChIA-PET data mediated by RNAP II,we find out the circRNAs whose flank introns have chromatin interaction,and compared with circRNAs whose flank introns are reverse complementary.In GM12878 cell line,we found that chromatin interaction between with flank introns have a significant impact on circRNA expression level,on the contrary,reverse complementary flank intron have no such effect.In K562,the host gene of circRNAs' degree in the RNAP II mediated chromatin interaction network is significantly lower compared with other types of genes,whereas the opposite was true in GM12878.Host gene-enriched KEGG pathways are related to Chronic myeloid leukemia,Colorectal cancer,Prostate cancer and other cancer.