Genome-Wide Analysis of Circular RNAs Reveals circCHRNG Regulates Sheep Myoblast Proliferation via miR-133/SRF and MEF2A Axis.

Yue Liu, Qian Chen, Jingjing Bao, Yabin Pu, Jianlin Han, Huijing Zhao, Yuehui Ma, Qianjun Zhao
Author Information
  1. Yue Liu: Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
  2. Qian Chen: Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
  3. Jingjing Bao: Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
  4. Yabin Pu: Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
  5. Jianlin Han: CAAS-ILRI Joint Laboratory on Livestock and Forage Genetic Resources, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing 100193, China.
  6. Huijing Zhao: Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
  7. Yuehui Ma: Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
  8. Qianjun Zhao: Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.

Abstract

As relatively new members of the non-coding RNA family, circRNAs play important roles in a variety of biological processes. However, the temporal expression pattern and the function of circRNAs during sheep skeletal muscle development remains unclear. This study aimed to identify circRNAs related to sheep skeletal muscle development and explore their roles in myoblast proliferation. The circRNA expression profiles of longissimus dorsi of sheep from F90, L30, and A3Y were obtained by the RNA-seq method. The function and mechanisms of the novel circCHRNG in muscle satellite cell proliferation were explored using CCK-8 assay, Western blot, qPCR, and dual-luciferase reporter assay. We identified 12,375 circRNAs, including 476, 133, and 233 DEcircRNAs found among three comparative groups. KEGG results showed that DEcircRNAs were enriched in muscle contraction, the regulation of cell proliferation, and the AMPK, insulin, and PI3K-Akt signaling pathways. Notably, a novel circRNA, termed circRNA CHRNG, acts as a miR-133 sponge to promote skeletal muscle satellite cell proliferation. Our study provides a systematic description of circRNAs of ovine skeletal muscle across fetal, lamb, and adult stages. GO and KEGG analyses showed that DEcircRNAs were enriched in multiple pathways associated with muscle development, such as the PI3K-Akt and AMPK signaling pathways. In addition, we propose that circCHRNG acts as a miR-133 sponge to upregulate the expression levels of SRF and MEF2A, thereby promoting myoblast proliferation.

Keywords

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Grants

  1. No.32172701/National Natural Science Foundation of China
  2. 2021YFD1300901/National Key R&D Program of China
  3. CARS-39-01/the Modern Wool Sheep Industry System

MeSH Term

Animals
Sheep
RNA, Circular
MicroRNAs
Proto-Oncogene Proteins c-akt
Phosphatidylinositol 3-Kinases
AMP-Activated Protein Kinases
Cell Proliferation
Myoblasts

Chemicals

RNA, Circular
MicroRNAs
Proto-Oncogene Proteins c-akt
Phosphatidylinositol 3-Kinases
AMP-Activated Protein Kinases

Word Cloud

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