College of Life Sciences, Xinyang Normal University, Xinyang, 464000, China.
Institute of Animal Science and Veterinary Medicine, Hainan Academy of Agricultural Sciences, Haikou, 571100, China.
Int J Biochem Cell Biol. 2018 Jun;99:211-218. doi: 10.1016/j.biocel.2018.04.016. Epub 2018 Apr 21.
Myoblast differentiation is a highly complex process that is regulated by proteins as well as by non-coding RNAs. Circular RNAs have been identified as an emerging new class of non-coding RNA in the modulation of skeletal muscle development, whereas their expression profiles and functional regulation in myoblast differentiation remain unknown. In the present study, we performed deep RNA-sequencing of C2C12 myoblasts during cell differentiation and uncovered 37,751 unique circular RNAs derived from 6943 hosting genes. The ensuing qRT-PCR and RNA fluorescence in situ hybridization verification were carried out to confirm the RNA-sequencing results. An unbiased analysis demonstrated dynamic circular RNA expression changes in the process of myoblast differentiation, and the circular RNA abundances were independent from their cognate linear RNAs. Gene ontology analysis showed that many down-regulated circular RNAs were exclusive to cell division and the cell cycle, whereas up-regulated circular RNAs were related to the cell development process. Furthermore, interaction networks of circular RNA-microRNA were constructed. Several microRNAs well-known for myoblast regulation, such as miR-133, miR-24 and miR-23a, were in this network. In summary, this study showed that circular RNA expression dynamics changed during myoblast differentiation. Circular RNAs play a role in regulating the myoblast cell cycle and development by acting as microRNA binding sites to facilitate their regulation of gene expression during myoblast differentiation. These findings open a new avenue for future investigation of this emerging RNA class in skeletal muscle growth and development.
肌母细胞分化是一个高度复杂的过程，受蛋白质和非编码 RNA 的调节。环状 RNA 已被确定为调节骨骼肌发育的新兴非编码 RNA 新类别，而它们在肌母细胞分化中的表达谱和功能调节仍不清楚。在本研究中，我们对 C2C12 肌母细胞在细胞分化过程中的深度 RNA 测序进行了分析，从 6943 个宿主基因中发现了 37751 个独特的环状 RNA。随后进行了 qRT-PCR 和 RNA 荧光原位杂交验证，以确认 RNA 测序结果。一项无偏分析表明，环状 RNA 在肌母细胞分化过程中的表达变化具有动态性，并且环状 RNA 的丰度与其同源线性 RNA 无关。基因本体分析表明，许多下调的环状 RNA 仅与细胞分裂和细胞周期有关，而上调的环状 RNA 则与细胞发育过程有关。此外，构建了环状 RNA-微小 RNA 的相互作用网络。一些已知对肌母细胞有调节作用的微小 RNA，如 miR-133、miR-24 和 miR-23a，都在这个网络中。综上所述，本研究表明，环状 RNA 的表达动态在肌母细胞分化过程中发生了变化。环状 RNA 通过充当微小 RNA 的结合位点，在调节肌母细胞细胞周期和发育中发挥作用，从而促进微小 RNA 对肌母细胞分化过程中基因表达的调节。这些发现为进一步研究这一新兴 RNA 类在骨骼肌生长和发育中的作用开辟了新的途径。
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