Post-Transcriptional Regulatory Network of Non-Coding RNAs in Yaks: Molecular Mechanisms of Hypoxia Adaptation and...

Yaks have long inhabited the Qinghai-Tibetan Plateau. This region features low-oxygen, frigid temperatures and pronounced seasonal variation in nutrient availability. They have evolved adaptive phenotypes centered on energy metabolism reprogramming, tissue structure remodeling, and stress homeostasis maintenance. In recent years, non-coding RNAs (ncRNAs) have been confirmed as an important component of the yak's post-transcriptional regulatory network. They play a key bridging role between environmental stress perception and phenotypic output through mechanisms such as influencing RNA splicing, stability, translation activity, and constructing competitive endogenous RNA (ceRNA) networks. This article systematically reviews the biogenesis pathways and core regulatory patterns of circular RNAs (circRNAs), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs). It focuses on summarizing the expression profile characteristics and dynamic spatiotemporal changes of these three types of ncRNAs in physiological contexts such as muscle and fat deposition, mammary gland lactation, testicular development, and hypoxia response in the heart, lungs, and vascular system of yaks. Current research evidence indicates that the regulatory network of yaks ncRNAs shows significant convergence on multiple key signaling pathways, mainly concentrating on lipid metabolism (PPAR/AMPK), nutrition and growth signals (PI3K-Akt/MAPK/mTOR), extracellular matrix remodeling (ECM-receptor interaction, Wnt/TGF-β), and cell stress fate determination (apoptosis, oxidative stress/ferroptosis) modules. Among them, some core circRNA and lncRNA-miRNA-mRNA regulatory axes have been functionally validated in vitro. Despite the phased progress, current research on ncRNA in yaks still faces bottlenecks: the multi-omics molecular atlases (encompassing genomics, transcriptomics, proteomics, and metabolomics) of key high-altitude adaptive organs remain incomplete, analysis processes lack sufficient standardization, and most studies stay at the association network level with limited causal mechanism validation. To address these limitations, future research should focus on building a standardized evidence chain, integrating multi-omics and single-cell/spatial transcriptome technologies, and conducting mechanism verification for traits in independent populations, thereby providing a solid theoretical basis for understanding the extreme environmental adaptation mechanisms of yaks and molecular breeding improvement.