Circular RNAs and host genes act synergistically in regulating cellular processes and functions in skeletal myogenesis

Abstract

Circular RNAs (circRNAs) are post-transcriptional regulators generated from backsplicing of pre-mRNAs of host genes. A major circRNA regulatory mechanism involves microRNA (miRNA) sequestering, relieving miRNA-blocked mRNAs for translation and functions. To investigate possible circRNA-host gene relationship, skeletal myogenesis is chosen as a study model for its developmental importance and for readily available muscle tissues from farm animals for studies at different myogenic stages. This review aims to provide an integrated interpretations on methodologies, regulatory mechanisms and possible host gene-circRNA synergistic functional relationships in skeletal myogenesis, focusing on myoblast differentiation and proliferation, core drivers of muscle formation in myogenesis, while other myogenic processes that play supportive roles in the structure, maintenance and function of muscle tissues are also briefly discussed. On literature review,thirty-two circRNAs derived from thirty-one host genes involved in various myogenic stages are identified; twenty-two (68.6 %) of these circRNAs regulate myogenesis by sequestering miRNAs to engage PI3K/AKT and other signaling pathways while four (12.5 %) are translated into proteins for functions. In circRNA-host gene relationship,ten (32.3 %) host genes are shown to regulate myogenesis,nine (29.0 %) are specific to skeletal muscle functions,and twelve (38.8 %) are linked to skeletal muscle disorders.Our analysis of skeletal myogenesis suggests that circRNAs and host genes act synergistically to regulate cellular functions. Such circRNA-host gene functional synergism may also be found in other major cellular processes. CircRNAs may have evolved later than miRNAs to counteract the suppressive effects of miRNAs and to augment host gene functions to further fine-tune gene regulation.

Keywords: CircRNA structure; MiRNA sponging; Muscular disorders; Myoblast differentiation; Satellite cells; Skeletal muscle; Skeletal myogenesis.