Assessment of myoblast circular RNA dynamics and its correlation with miRNA during myogenic differentiation
Assessment of myoblast circular RNA dynamics and its correlation with miRNA during myogenic differentiation
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成肌分化过程中成肌细胞环状RNA动力学及其与miRNA的相关性评估
DOI：
10.1016/j.biocel.2018.04.016
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发表时间：
2018
影响因子：
4
通讯作者：
Xu YJ
中科院分区：
文献类型：
--
作者：
Zhang Pengpeng;Xu Haixia;Li Rui;Wu Wei;Li Cencen;Wang Lei;Xu Yongjie;Chao Zhe;Xia Wei;Yang Jinzeng;Xu YJ
成肌细胞分化是一个高度复杂的过程，受蛋白质和非编码rna的调控。环状RNA已被确定为一种新兴的非编码RNA，在骨骼肌发育的调节中，然而其表达谱和成肌细胞分化的功能调控尚不清楚。在本研究中，我们对细胞分化过程中的C2C12成肌细胞进行了深度rna测序，发现了来自6943个宿主基因的37,751个独特的环状rna。随后进行qRT-PCR和RNA荧光原位杂交验证，以确认RNA测序结果。无偏分析表明，在成肌细胞分化过程中，环状RNA的表达发生了动态变化，其丰度与同源线性RNA无关。基因本体分析表明，许多下调的环状rna只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，我们还构建了环状rna -微rna的相互作用网络。几个众所周知的用于成肌细胞调控的microrna，如miR-133、miR-24和miR-23a，都在这个网络中。综上所述，本研究表明，在成肌细胞分化过程中，环状RNA的表达动态发生了变化。环状rna作为microRNA结合位点，在成肌细胞分化过程中调控基因表达，在成肌细胞周期和发育中发挥重要作用。这些发现为未来研究这类新兴RNA在骨骼肌生长发育中的作用开辟了新的途径。
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 fluorescencein situhybridization 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.