Chen Mingming, Lian Di, Li Yan, Zhao Yue, Xu Xueling, Liu Zhimei, Zhang Jinlong, Zhang Xiaosheng, Wu Sujun, Qi Shiyu, Deng Shoulong, Yu Kun, Lian Zhengxing
Beijing Key Laboratory for Animal Genetic Improvement, National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University, Beijing, China.
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.
DNA Cell Biol. 2023 Mar;42(3):163-175. doi: 10.1089/dna.2022.0574.
Improving livestock and poultry growth rates and increasing meat production are urgently needed worldwide. Previously, we produced a myostatin (MSTN) and fibroblast growth factor 5 (FGF5) double-knockout (MF) sheep by CRISPR Cas9 system to improve meat production, and also wool production. Both MF sheep and the F1 generation (MF) sheep showed an obvious "double-muscle" phenotype. In this study, we identified the expression profiles of long noncoding RNAs (lncRNAs) in wild-type and MF sheep, then screened out the key candidate lncRNAs that can regulate myogenic differentiation and skeletal muscle development. These key candidate lncRNAs can serve as critical gatekeepers for muscle contraction, calcium ion transport and skeletal muscle cell differentiation, apoptosis, autophagy, and skeletal muscle inflammation, further revealing that lncRNAs play crucial roles in regulating muscle phenotype in MF sheep. In conclusion, our newly identified lncRNAs may emerge as novel molecules for muscle development or muscle disease and provide a new reference for MSTN-mediated regulation of skeletal muscle development.
提高畜禽生长速度和增加肉类产量在全球范围内都迫切需要。此前，我们通过CRISPR Cas9系统培育出了一种肌肉生长抑制素（MSTN）和成纤维细胞生长因子5（FGF5）双敲除（MF）绵羊，以提高肉类产量，同时也提高羊毛产量。MF绵羊及其F1代（MF）绵羊均表现出明显的“双肌”表型。在本研究中，我们鉴定了野生型和MF绵羊中长链非编码RNA（lncRNA）的表达谱，然后筛选出了能够调节肌源性分化和骨骼肌发育的关键候选lncRNA。这些关键候选lncRNA可作为肌肉收缩、钙离子转运以及骨骼肌细胞分化、凋亡、自噬和骨骼肌炎症的关键调控因子，进一步揭示lncRNA在调节MF绵羊肌肉表型中发挥着关键作用。总之，我们新鉴定出的lncRNA可能成为肌肉发育或肌肉疾病的新型分子，并为MSTN介导的骨骼肌发育调控提供新的参考。
