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

Lnc-MEG8 通过 miR-22-3p/RTL1 轴调控牦牛成肌细胞分化

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作者:Xiaoming Ma, Yongfu La, Tong Wang, Chun Huang, Fen Feng, Xian Guo, Pengjia Bao, Xiaoyun Wu, Min Chu, Chunnian Liang, Ping Yan1

Background

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.

Conclusion

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.

Results

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.

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