Integrated Multi-Omics Analysis For Decoding The Roles Of ILF3 In RNA Regulation

Double-stranded RNA binding protein ILF3 is widely found in animals and is involved in several important biological processes including transcriptional regulation,miRNA biogenesis,RNA stability and response to viral infection.Although some studies on ILF3 protein have been reported,due to the complexity of its structure and biological functions,the targets and regulatory roles of ILF3 protein are still unclear.In this study,we target the roles of ILF3 protein for RNA regulation,optimized the CLIP-seq and small RNA-seq technologies,integratedly analyzed multi-omics data including RNA-seq,small RNA-seq,CLIP-seq and ChIP-seq,thus comprehensively decoded the targets and biological functions of ILF3 protein in cells.We obtained a more accurate RNA binding map of ILF3 in the nucleus from nuclear CLIP-seq data.We utilized spike-in in small RNAseq for data normalization,and found that ILF3 may inhibit the expression of some miRNAs.We analyzed RNA-seq data upon ILF3 knockown,and found that many genes were down-regulated and these genes were highly associated with damage repair and antiviral infection pathways.ChIP-seq data analysis showed that ILF3 was significantly enriched in the promoter regions,indicating that ILF3 may regulate gene expression at the transcriptional level.Finally,we analyzed the roles of ILF3 protein in regulating RNA alterantive splicing based on the RNA-seq data.In sum,we integratedly analyzed multi-omics data of ILF3 from different highthroughput technologies to decode the biological functions of ILF3 protein at both transcriptional and post-transcriptional levels.The results provided the diverse regulated RNA events by ILF3 protein,which are useful for comprehensively understanding the biological functions and mechanisms of ILF3 in cells.