Circular RNA circMYBPC1 promotes skeletal muscle differentiation by targeting MyHC

Abstract

Skeletal muscle development is a complex and highly orchestrated biological process mediated by a series of myogenesis regulatory factors. Numerous studies have demonstrated that circular RNAs (circRNAs) are involved in muscle differentiation, but the exact molecular mechanisms involved remain unclear. Here, we analyzed the expression of circRNAs at the adult and embryo development stages of cattle musculus longissimus . A stringent set of 1,318 circRNAs candidates were identified, and we found that 495 circRNAs were differentially expressed between embryonic and adult tissue libraries. We subsequently focused on one of the most downregulated circRNAs (using the adult stage expression as control), and this was named muscle differentiation-associated circular RNA (circMYBPC1). With RNA binding protein immunoprecipitation (RIP) and RNA pull-down assays, circMYBPC1 was identified to promote myoblast differentiation by directly binding miR-23a to relieve its inhibition on myosin heavy chain ( MyHC ). In addition, RIP assays demonstrated that circMYBPC1 could directly bind MyHC protein. In vivo observations also suggested that circMYBPC1 may stimulate skeletal muscle regeneration after muscle damage. These results revealed that the novel non-coding circRNA circMYBPC1 promotes differentiation of myoblasts and may promote skeletal muscle regeneration. Our results provided a basis for in-depth analysis of the role of circRNA in myogenesis and muscle diseases.

circTAF8 Regulates Myoblast Development and Associated Carcass Traits in Chicken

“…Muscle development is a complex process precisely regulated by specific genes and signaling pathways ( Houba et al, 2004 ; Grefte et al, 2007 ). CircRNAs, as a new type of posttranscriptional regulator in skeletal muscle, have also been discovered in rhesus monkeys, mice, pigs, cattle, and sheep ( Huang et al, 2018 ; Xu et al, 2018 ; Hao et al, 2020 ; Chen et al, 2021 ). Our previous studies have shown that circRNAs are abundantly and dynamically expressed during chicken muscle development ( Ouyang et al, 2018b ).…”

“…Our results showed that circTAF8 is mainly present in the cytoplasm. Multiple reports have found that most circRNAs that are related to skeletal muscle and function as miRNA sponges are located in the cytoplasm ( Ouyang et al, 2018a ; Chen et al, 2019 ; Chen et al, 2021 ). These results indicate that circTAF8 was reliable and stable in chicken muscle.…”

“…A priori power analyses were performed using G*Power software version 3.1.9.7 (Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany) ( Faul et al, 2009 ) based on the effect size and standard deviation of a previous publication ( Chen et al, 2021 ) or preliminary data to achieve a significance level (α) of 0.05 and a power of 0.8. In this study, three biological replicates were included in the analyses unless stated otherwise.…”

“…CircRNAs are widely present in eukaryotic animals and participate in various biological processes. Studies have found that circRNAs are closely related to myogenesis, the transformation of muscle fiber types, and skeletal muscle diseases ( Kyei et al, 2020 ; Li et al, 2020 ; Chen et al, 2021 ). Our group has previously reported that circSVIL ( Ouyang et al, 2018a ), circHIPK3 ( Chen et al, 2019 ), and circFGFR2 ( Chen et al, 2018 ) promote the proliferation and differentiation of chicken myoblasts.…”

The Circular RNA CircCOL1A1 Functions as a miR-149-5p Sponge to Regulate the Formation of Superior-Quality Brush Hair via the CMTM3/AR Axis

“…CircAGFG1 accelerates the proliferation, migration and invasion of breast cancer cells by sponging miR-195-5p (Yang et al, 2019). In livestock, circTTN and circMYBPC1 have been identified as ceRNAs that sponge miRNAs and modulate skeletal muscle development Chen et al, 2021); circHIPK3 plays a critical role in the cow mammary gland to influence milk production by regulating the signal transducer and activator of transcription 5 (STAT5) signaling pathway (Liu et al, 2020). However, little is known about circRNA functions in Yangtze River Delta white goats and the regulatory mechanism involved in superior-quality brush hair formation.…”