Comprehensive CircRNA Profiling and Selection of Key CircRNAs Reveal the Potential Regulatory Roles of CircRNAs throughout Ovarian Development and Maturation in Cynoglossus semilaevis

Abstract

CircRNAs are novel endogenous non-coding small RNAs involved in the regulation of multiple biological processes. However, little is known regarding circRNAs in ovarian development and maturation of fish. Our study, for the first time, provides the genome-wide overview of the types and relative abundances of circRNAs in tongue sole tissues during three ovarian developmental stages. We detected 6790 circRNAs in the brain, 5712 in the pituitary gland, 4937 in the ovary and 4160 in the liver. Some circRNAs exhibit tissue-specific expression, and qRT-PCR largely confirmed 6 differentially expressed (DE) circRNAs. Gene Ontology and KEGG pathway analyses of DE mRNAs were performed. Some DE circRNA parental genes were closely associated with biological processes in key signalling pathways and may play essential roles in ovarian development and maturation. We found that the selected circRNAs were involved in 10 pathways. RNase R digestion experiment and Sanger sequencing verified that the circRNA had a ring structure and was RNase R resistant. qRT-PCR results largely confirmed differential circRNA expression patterns from the RNA-seq data. These findings indicate that circRNAs are widespread in terms of present in production-related tissues of tongue sole with potentially important regulatory roles in ovarian development and maturation.

CircRNA Identification and CircRNA–miRNA–mRNA Network in Cynoglossus semilaevis Sexual Size Dimorphism

“…Given that most circRNAs are generally produced from pre-mRNA back-splicing [ 24 ], the reason for there being few circRNAs in the W chromosome may be attributed to the fact that the W chromosome of C. semilaevis has the least number of functional genes (317), accounting for 17–34% of other chromosomes [ 9 ]. As in previous studies [ 43 , 57 , 58 , 59 ], the C. semilaevis circRNAs exhibited obvious tissue and sex-specific expression patterns, with gonads showing the largest number of differentially expressed circRNAs in different genders.…”

“…In mammals, birds, and teleosts, it was reported that circRNA plays important roles in muscle growth regulation [ 41 , 68 , 69 , 70 ]. Moreover, there are also studies addressing the involvement of circRNAs in the ovary development and sex determination for birds and teleosts [ 43 , 44 , 71 ]. Therefore, the present study not only enriches the potential roles of circRNA in physiological processes, but it also provides new clues for the explanation of fish SSD.…”

“…In teleosts such as the large yellow croaker ( Larimichthys crocea ), the grass carp ( Ctenopharyngodon idellus ), and the Nile tilapia ( Oreochromis niloticus ), circRNAs have been identified to be involved in growth, immunity, and heat stress [ 36 , 37 , 38 , 39 , 40 , 41 ]. In C. semilaevis , circRNA has been reported to regulate sex determination and differentiation [ 42 , 43 , 44 ]. However, there is no research on the roles of circRNA on Chinese tongue sole SSD.…”

Potential Clinical Applications of Exosomal Circular RNAs: More than Diagnosis

“…Evidence has revealed that circRNAs display various functions by behaving as gene expression modulators (Jiao et al, 2021), serving as miRNA sponges (Kumar et al, 2017), interacting with proteins (Mo et al, 2021), regulating transcription (Verduci et al, 2021) and translated into proteins (Fontemaggi et al, 2021) ( Figure 1 ). Since exosomes and their biologically active cargoes may offer prognostic information in a range of diseases, as one of their cargo components circRNAs have become a research hotspot in recent years because of their close relation with the development of diseases ( Li et al, 2021 ). These molecules are characterized by a covalently closed loop configuration created through a back-splicing occasion whereby a 3′-5′ phosphodiester bond is formed ( Deng et al, 2019 ).…”