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

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.