CircRRAS2 promotes myogenic differentiation of bovine MuSCs and is a novel regulatory molecule of muscle development

Abstract

The proliferation and myogenic differentiation of muscle stem cells (MuSCs) are important factors affecting muscle development and beef quality. There is increasing evidence that circRNAs can regulate myogenesis. We found a novel circRNA, named circRRAS2 that is significantly upregulated in the differentiation phase of bovine MuSCs. Here, we aimed to determine its roles in the proliferation and myogenic differentiation of these cells. The results showed that circRRAS2 was expressed in several bovine tissues. CircRRAS2 inhibited MuSCs proliferation and promoted myoblast differentiation. In addition, chromatin isolation by using RNA purification and mass spectrometry in differentiated muscle cells identified 52 RNA-binding proteins that could potentially bind to circRRAS2, in order to regulate their differentiation. The results suggest that circRRAS2 could be a specific regulator of myogenesis in bovine muscle.

Highlights

• CircRRAS2 expression is higher in DM cells than in GM cells.

• CircRRAS2 could significantly inhibit the proliferation and apoptosis of bovine MuSCs.

• CircRRAS2 promotes the differentiation of bovine MuSCs into myotubes.

• CircRRAS2 may exert regulatory effects through multiple RNA binding proteins.

Keywords:

• CircRRAS2
• muscle stem cells
• myogenesis
• differentiation
• RNA-binding proteins

Acknowledgments

The authors also thank Dr. Dev Sooranna, Imperial College London, for editing the manuscript.

Ethical approval

This study was approved by the Ethics Committee of Guangxi University, Nanning, Guangxi, China (SYXK2020-0004).

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The research was funded by the National Natural Science Foundation of China [grant no. 31860644], National Key Research and Development Program of China [grant no. 2021YFD1100100], Natural Science Foundation of Guangxi Province [grant nos. 2021JJD130097, 2022GXNSFDA035064, AB19245010 and 2019GXNSFDA185002], Guangxi Innovation Team Construction Project of National Modern Agricultural Industry Technology System [grant no. nycytxgxcxtd-2021-09-01] and Bama County Program for Talents in Science and Technology [grant no. 202101263].