Lnc-MEG8 regulates yak myoblast differentiation via the miR-22-3p/RTL1 axis

• Published in: BMC genomics 2024-11, Vol.25 (1), p.1146-15, Article 1146
• Main Authors: Ma, Xiaoming, La, Yongfu, Wang, Tong, Huang, Chun, Feng, Fen, Guo, Xian, Bao, Pengjia, Wu, Xiaoyun, Chu, Min, Liang, Chunnian, Yan, Ping
• Format: Article
• Language: English
• Subjects: Animal husbandry; Animals; Atrophy; Bos grunniens; Care and treatment; Cattle; Cell differentiation; Cell Differentiation - genetics; Cell growth; Cell Proliferation; Chromosome 3; Competition; Cytoplasm; Diagnosis; Differentiation; Diseases; Fibroblasts; Gene Expression Profiling; Genes; Genetic aspects; Growth; Health aspects; High altitude; Livestock; Lnc-MEG8; Localization; Medical examination; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; MiR-22-3p; Muscle Development - genetics; Muscle diseases; Muscle, Skeletal - cytology; Muscle, Skeletal - metabolism; Muscles; Musculoskeletal system; Myoblasts; Myoblasts - cytology; Myoblasts - metabolism; Myotubes; Proteins; RNA; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; RTL1; Skeletal muscle; Skeletal myoblasts; Stem cells; Tissue engineering; Transcriptomes; Transfection; Yak; Yaks
• ISSN: 1471-2164; 1471-2164
• DOI: 10.1186/s12864-024-11038-y

The yak (Bos grunniens) is essential to the livelihoods of Tibetan people on the Qinghai-Tibet Plateau; however, its growth and productivity are constrained by the region's harsh climate and high altitude. Yak skeletal muscle myoblasts, which have evolved to thrive under these challenging conditions, offer a valuable model for investigating muscle development. In this study, we performed transcriptome profiling of yak longissimus dorsi muscle at different growth stages, identifying a key long non-coding RNA, LncRNA-XR_314844 (Lnc-MEG8), with a potential role in muscle development. We developed a novel technique to isolate high-quality yak myoblasts, enabling detailed analysis of Lnc-MEG8. Our results indicated that Lnc-MEG8's subcellular localization varies during muscle cell growth: it is found in both the nucleus and cytoplasm during proliferation but shifts mainly to the cytoplasm during differentiation. Functional experiments showed that Lnc-MEG8 promotes cell proliferation and inhibits differentiation, while its silencing had the opposite effect. Further analysis revealed that both Lnc-MEG8 and the gene RTL1 share miR-22-3p as a common target. Dual-luciferase assays confirmed miR-22-3p directly targets both Lnc-MEG8 and RTL1 mRNA. Co-transfection of Lnc-MEG8 and a miR-22-3p mimic restored RTL1 expression, highlighting Lnc-MEG8's regulatory role. Lnc-MEG8 also counteracts miR-22-3p's suppression of key muscle genes such as MyF5 and MyoG, facilitating myotube formation. These findings demonstrate that the Lnc-MEG8-miR-22-3p-RTL1 axis plays a crucial role in yak muscle development, providing insights that could advance muscle tissue engineering and enhance yak meat quality.