Abstract
BACKGROUND: Circular RNA (circRNA), as a new members of noncoding RNA family, have vital functions in many biological processes by as microRNA sponges or competing endogenous RNAs (ceRNAs). However, little has been reported about the genetic mechanism of circRNAs regulation of feed efficiency in sheep. RESULTS: This study aimed to explore the expression of circRNAs in the liver of Hu sheep with High-RFI (High residual feed intake) and Low-RFI (Low residual feed intake) using transcriptome sequencing. A total of 20,729 circRNAs were identified in two groups, in which 219 circRNAs were found as significantly differentially expressed. Several circRNAs were validated by using RT-PCR, sanger sequencing and RT-qPCR methods. These results demonstrated that the RNA-seq result and expression level of circRNAs identified are reliable. Subsequently, GO and KEGG enrichment analysis of the parental genes of the differentially expressed (DE) circRNAs were mainly involved in immunity response and metabolic process. Finally, the ceRNA regulatory networks analysis showed that the target binding sites for miRNA such as novel_41, novel_115, novel_171 and oar-miR-485-3p in the identified DE cirRNAs. Importantly, two metabolic (SHISA3 and PLEKHH2) and four (RTP4, CD274, OAS1, and RFC3) immune-related target mRNAs were identified from 4 miRNAs. Association analysis showed that the polymorphism (RTP4 c.399 A > G) in the target gene RTP4 were significantly associated with RFI (P < 0.05). CONCLUSIONS: Analysis of sequencing data showed some candidate ceRNAs that may play key roles in the feed efficiency in sheep by regulating animal immune and metabolic. These results provide the basis data for further study of the biological functions of circRNAs in regulating sheep feed efficiency.