CircRtn4 Acts as the Sponge of miR-24-3p to Promote Neurite Growth by Regulating CHD5.
CircRtn4 Acts as the Sponge of miR-24-3p to Promote Neurite Growth by Regulating CHD5.
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CircRtn4 作为 miR-24-3p 的海绵，通过调节 CHD5 促进神经突生长
DOI：
10.3389/fnmol.2021.660429
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发表时间：
2021
影响因子：
4.8
通讯作者：
Wan J
中科院分区：
文献类型：
--
作者：
Qi Y;Ma N;Chen X;Wang Y;Zhang W;Wan J
环状RNA(CircRNAs)是共价闭合的单链RNA分子。CircRNAs来源于前体mRNA的反向剪接，在许多生物过程中发挥着重要的作用。最近的研究表明，哺乳动物大脑中存在多种功能不明确的CircRNA。CircRtn4在小鼠脑内的表达随着原代神经元的分化而增加。在我们的研究中，CircRtn4基因的敲除抑制了轴突的生长，而CircRtn4的过表达显著增加了轴突的长度。通过双荧光素酶报告实验和RNA反义纯化实验，初步确定CircRtn4为miR-24-3p的miRNA海绵。此外，miR-24-3p基因敲除增加了神经突起的长度，而miR-24-3p基因的过表达显著抑制了神经突起的生长。进一步证实CHD5是miR-24-3p的下游靶基因。CHD5的沉默抵消了CircRtn4过表达对轴突生长的积极作用。综上所述，CircRtn4可能作为miR-24-3p的海绵，通过调节CHD5促进轴突生长。
Circular RNAs (circRNAs) are covalently closed single-stranded RNA molecules. After derived from precursor mRNA back-splicing, circRNAs play important roles in many biological processes. Recently, it was shown that several circRNAs were enriched in the mammalian brain with unclear functions. The expression of circRtn4 in the mouse brain was increased with the differentiation of primary neurons. In our study, knockdown of circRtn4 inhibited neurite growth, while overexpression of circRtn4 significantly increased neurite length. By dual-luciferase reporter assay and RNA antisense purification assay, circRtn4 was identified as a miRNA sponge for miR-24-3p. Moreover, knockdown of miR-24-3p increased neurite length, while overexpression of miR-24-3p significantly inhibited neurite growth. Furthermore, CHD5 was confirmed to be a downstream target gene of miR-24-3p. And CHD5 silence counteracted the positive effect of circRtn4 overexpression on neurite growth. In conclusion, circRtn4 may act as the sponge for miR-24-3p to promote neurite growth by regulating CHD5.
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