Circular RNAs in Muscle Function and Disease

Abstract

Circular RNAs (circRNAs) are a class of RNA produced during pre-mRNA splicing that are emerging as new members of the gene regulatory network. In addition to being spliced in a linear fashion, exons of pre-mRNAs can be circularized by use of the 3′ acceptor splice site of upstream exons, leading to the formation of circular RNA species. In this way, genetic information can be re-organized, increasing gene expression potential. Expression of circRNAs is developmentally regulated, tissue and cell-type specific, and shared across eukaryotes. The importance of circRNAs in gene regulation is now beginning to be recognized and some putative functions have been assigned to them, such as the sequestration of microRNAs or proteins, the modulation of transcription, the interference with splicing, and translation of small proteins. In accordance with an important role in normal cell biology, circRNA deregulation has been reported to be associated with diseases. Recent evidence demonstrated that circRNAs are highly expressed in striated muscle tissue, both skeletal and cardiac, that is also one of the body tissue showing the highest levels of alternative splicing. Moreover, initial studies revealed altered circRNA expression in diseases involving striated muscle, suggesting important functions of these molecules in the pathogenetic mechanisms of both heart and skeletal muscle diseases. The recent findings in this field will be described and discussed.

Exosomes are the novel players involved in the beneficial effects of exercise on type 2 diabetes

“…In addition, lncRNA H19, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), MD1, and MyoD in skeletal muscles, respectively, sponge miR-675, Let-7 family, miR-133, and protein IMP2 to mediate myogenesis (Dey, Pfeifer, & Dutta, 2014;Gong et al, 2015;Han, Yang, Cao, & Liang, 2015;Legnini, Morlando, Mangiavacchi, Fatica, & Bozzoni, 2014). CircRNAs such as circ-ZNF609, circ-QKI, and circ-BNC2 from skeletal muscle, respectively, regulates myoblast proliferation and differentiation (Greco, Cardinali, Falcone, & Martelli, 2018;Legnini et al, 2017) by interacting with miR-133, miR-24, and miR-23 (P. . from pancreas has been shown to enhance insulin secretion via repressing miR-7 (Xu, Guo, Li, & Yu, 2015).…”

CircRIMKLB Promotes Myoblasts Proliferation and Inhibits Differentiation via Sponging miR-29c to Release KCNJ12

“…According to their sources, circular RNAs can be divided into three types, exonic circRNAs, intronic circRNAs and exonicintronic circRNAs [14,15]. In general, most exonic circRNAs are localized in the cytoplasm and could function as a sponge for miRNAs to affect post-transcriptional regulation, which means that circRNAs could be a member of competing endogenous RNAs (ceRNAs) [16]. For instance, ciRS-7/CDR1 is regarded as the inhibitor of miR-7 to regulate hepatocellular carcinoma [17].…”

“…It has been found that CircRNAs are highly enriched in striated muscle, indicating that circRNAs service as a new regulatory network that contributes to skeletal muscle development, myogenesis and regeneration, etc. [16]. However, the existing research on how circular RNA affecting muscle development is relatively rare, so the study on circular RNA can help to gain a deeper understanding of the regulatory network for muscle development.…”

The roles of circRFWD2 and circINO80 during NELL‐1‐induced osteogenesis

“…High throughput sequencing has demonstrated that circRNAs were widely and abundantly distributed in the eukaryotic transcriptome with tissue‐specific expression . Functionally, circRNAs could regulate the protein function via cap‐independent mechanism, affect the splicing of parental genes and serve as the microRNAs (miRNAs) sponges to cross‐talk with miRNAs . Emerging evidence has proven that circRNAs played important roles in the development of normal tissues and various diseases, such as cardiovascular diseases, age‐related diseases, autoimmune diseases and tumours .…”

“…20 Functionally, circRNAs could regulate the protein function via cap-independent mechanism, affect the splicing of parental genes and serve as the microRNAs (miRNAs) sponges to cross-talk with miRNAs. [21][22][23] Emerging evidence has proven that cir-cRNAs played important roles in the development of normal tissues and various diseases, such as cardiovascular diseases, age-related diseases, autoimmune diseases and tumours. [24][25][26][27][28][29][30] Their functions as potential biomarkers were gradually discovered in cancers and neurodegenerative disorders.…”