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Background: Yaks (Bos grunniens), prized for their ability to thrive in high-altitude environments, are indispensable livestock in the plateau region. Modifying their feeding systems holds significant promise for improving their growth and meat quality. Tenderness, a key determinant of yak meat quality and consumer appeal, is demonstrably influenced by dietary regimen. Indoor feeding regimes have been shown to enhance tenderness by lowering shear stress and optimizing pH values. CircRNAs, well-known modulators of circulatory function, also play a crucial role in skeletal muscle development across various animal species. However, their functional significance in yak skeletal muscle remains largely unexplored. Results: In this study, we identified a total of 5,534 circRNAs within the longissimus dorsi muscle, and we found 51 differentially expressed circRNAs (20 up-regulated and 31 down-regulated) between the two feeding groups. Constructing a comprehensive ceRNA network illuminated intricate regulatory mechanisms, with PGP and circRNA_0617 converging on bta-miR-2285q, mirrored by KLF15/circRNA_0345/bta-miR-20b and CTSF/circRNA_0348/bta-miR-146a. These findings shed light on the potential of circRNAs to influence yak muscle development and meat quality, offering valuable insights for future research. Conclusions: This investigation unraveled a complex interaction network between circRNAs、mRNAs and miRNAs in yak skeletal muscle. We further elucidated the target genes regulated by these target genes within the network, offering valuable insights into the potential regulatory mechanisms governing muscle development and meat quality-related traits in yaks. [ABSTRACT FROM AUTHOR]

Simple Summary: The aim of our study was to investigate the effects of dietary supplementation with different protein levels after grazing on growth performance as well as on the proteomics of the LL muscle of Jersey-yak. The results showed that a certain amount of crude protein supplementation to Jersey-yak at the end of grazing significantly improved growth performance and increased their economic efficiency. In addition, we analyzed the proteomic differences in the longest dorsal muscle of Jersey-yak. From our analyses, we identified differences in the abundance of 434 proteins involved in pathways related to muscle growth and development and energy metabolism, among others. Several of the proteins enriched in these pathways, such as MYH8, are associated with myoblast development and differentiation as well as muscle development. In conclusion, the results of this study provide proteomic insights into the different feeding patterns of yak crossbred progeny, suggesting that a greater economic income can be achieved by improving their feeding conditions. Jersey-yak is a hybrid offspring of Jersey cattle and yak (Bos grunniens). Changing the feeding system of Jersey-yak can significantly improve its growth performance. In this study, tandem mass tag (TMT) proteomics technology was used to determine the differentially expressed proteins (DEPs) of the longissimus lumborum (LL) muscle of Jersey-yak fed different protein levels of diet. The results showed that compared with the traditional grazing feeding, the growth performance of Jersey-yaks was significantly improved by crude protein supplementation after grazing. A total of 3368 proteins were detected in these muscle samples, of which 3365 were quantified. A total of 434 DEPs were identified. Through analyses, it was found that some pathways related to muscle growth and development were significantly enriched, such as Rap1 signaling pathway, mTOR signaling pathway, and TGF-beta signaling pathway. A number of DEPs enriched in these pathways are related to muscle cell development, differentiation, and muscle development, including integrin subunit alpha 7 (ITGA7), myosin heavy chain 8 (MYH8), and collagen type XII alpha 1 chain (COL12A1). In conclusion, the results of this study provide insights into the proteomics of different feeding patterns of Jersey-yak, providing a stronger basis for further understanding the biological mechanism of hybrid varieties. [ABSTRACT FROM AUTHOR]

Cattle-yak is a hybrid F1 generation of cattle and yak, which has a history of more than 3000 years and has shown better production performance and higher economic benefits than those of yaks. However, up to now, there has been no study on the transcriptome-wide m6A methylation profile of bovine skeletal muscle and its potential biological function during muscle development. Here, we observed significant changes in the expression levels of muscle-related marker genes and methylation-related enzymes during the development of cattle-yak, and the overall m6A content in the Longissimus dorsi muscle of 18-month-old cattle-yak decreased significantly. A total of 36,602 peaks, 11,223 genes and 8388 lncRNAs were identified in the two groups, including 2989 differential peaks (427 up-regulated peaks and 2562 down-regulated peaks), 1457 differentially expressed genes (833 up-regulated genes and 624 down-regulated genes) and 857 differentially expressed lncRNAs (293 up-regulated lncRNAs and 564 down-regulated lncRNAs). GO and KEGG analysis revealed that they were significantly enriched in some muscle-related pathways (Wnt signaling pathway and MAPK signaling pathway) and high-altitude adaptation-related pathway (HIF-1 signaling pathway). Moreover, m6A abundance was positively correlated with gene expression levels, while it was negatively correlated with lncRNA expression levels. This indicates that m6A modification played an important role in the Longissimus dorsi muscle development of cattle-yak; however, the regulation mechanism of m6A-modified mRNA and lncRNA may be different. This study was the first report of transcriptome-wide m6A-modified mRNAs and lncRNAs atlas in the Longissimus dorsi muscle development of cattle-yak, one which will provide new perspectives for genetic improvement in bovines. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) have been extensively studied in recent years. Numerous lncRNAs have been identified in mice, rats, and humans, some of which play important roles in muscle formation and development. However, little is known about lncRNA regulators that affect muscle development in yak (Bos grunniens). LncRNA expression during skeletal muscle development in yak was analyzed by RNA sequencing at three development stages: 3 years (group A), 6 months (group M), and 90-day-old fetuses (group E). A total of 1180 lncRNAs were identified in the three development stages. Compared with group E, 154 were upregulated and 130 were downregulated in group A. Compared with group A, 31 were upregulated and 29 were downregulated in group M. Compared with group E, 147 were upregulated and 149 were downregulated in group M (padj < 0.001, |log2FC| > 1.2). In addition, functional annotation analysis based on gene ontology (GO) and the Kyoto protocol encyclopedia of genes and genomes (KEGG) database showed that differentially expressed lncRNAs (DElncRNAs) were cis–trans target genes. The results showed that DElncRNAs were mainly involved in PI3K-Akt signaling pathway, focal adhesion, MAPK signaling pathway, apoptosis, and p53 signaling pathway. Furthermore, RTL1, IGF2, MEF2C, Pax7, and other well-known muscle development regulators were included in a co-expression network of differentially expressed target genes and lncRNAs. These data will help to further clarify the function of lncRNAs in the different stages of skeletal muscle developmental in yak. [ABSTRACT FROM AUTHOR]

DNA methylation modifications are implicated in many biological processes. As the most common epigenetic mechanism DNA methylation also affects muscle growth and development. The majority of previous studies have focused on different varieties of yak, but little is known about the epigenetic regulation mechanisms in different age groups of animals. The development of muscles in the different stages of yak growth remains unclear. In this study, we selected the longissimus dorsi muscle tissue at three different growth stages of the yak, namely, 90-day-old fetuses (group E), six months old (group M), and three years old (group A). Using RNA-Seq transcriptome sequencing and methyl-RAD whole-genome methylation sequencing technology, changes in gene expression levels and DNA methylation status throughout the genome were investigated during the stages of yak development. Each group was represented by three biological replicates. The intersections of expression patterns of 7694 differentially expressed genes (DEGs) were identified (padj < 0.01, |log2FC| > 1.2) at each of the three developmental periods. Time-series expression profile clustering analysis indicated that the DEGs were significantly arranged into eight clusters which could be divided into two classes (padj < 0.05), class I profiles that were downregulated and class II profiles that were upregulated. Based on this cluster analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that DEGs from class I profiles were significantly (padj < 0.05) enriched in 21 pathways, the most enriched pathway being the Axon guidance signaling pathway. DEGs from the class II profile were significantly enriched in 58 pathways, the pathway most strongly enriched being Metabolic pathway. After establishing the methylation profiles of the whole genomes, and using two groups of comparisons, the three combinations of groups (M-vs.-E, M-vs.-A, A-vs.-E) were found to have 1344, 822, and 420 genes, respectively, that were differentially methylated at CCGG sites and 2282, 3056, and 537 genes, respectively, at CCWGG sites. The two sets of data were integrated and the negative correlations between DEGs and differentially methylated promoters (DMPs) analyzed, which confirmed that TMEM8C, IGF2, CACNA1S and MUSTN1 were methylated in the promoter region and that expression of the modified genes was negatively correlated. Interestingly, these four genes, from what was mentioned above, perform vital roles in yak muscle growth and represent a reference for future genomic and epigenomic studies in muscle development, in addition to enabling marker-assisted selection of growth traits. [ABSTRACT FROM AUTHOR]

Cattle-yak, which is the hybrid F 1 generation of cattle and yak, demonstrates better production performance compared to yak. However, there is limited research on the molecular mechanisms responsible for the muscle development of cattle-yak. To address this knowledge gap, a comprehensive transcriptomic survey of the longissimus dorsi muscle in cattle-yak was conducted. Three transcript types, namely lncRNAs, miRNAs, and circRNAs, along with protein-coding genes were characterized at two developmental stages (6 m, 18 m) of cattle-yak. The results revealed significant enrichment of these transcripts into pathways related to myoblast differentiation and muscle development signaling. Additionally, the study identified the TCONS00024465/circHIPK3-bta-miR-499- ADAMTS6 regulatory network, which may play a crucial role in the muscle development of cattle-yak by combining the transcriptome data of yak and constructing the ceRNA co-expression network. HEK 293 T cells were used to validate that TCONS00024465 and circHIPK3 are located upstream of bta-miR-499, and can competitively bind to bta-miR-499 as ceRNA. The study also verified that ADAMTS6 regulates skeletal muscle development by inhibiting myoblast proliferation, promoting myoblast differentiation, and positively regulating the apoptosis of myoblasts. Taken together, this study provides new insights into the advantages of cattle-yak production performance and offers a molecular basis for further research on muscle development. • Cattle-yak, as the hybrid animal, exhibits better production performance compared to yak. • The first transcriptome profile of cattle-yak revealed the key role of TCONS00024465/circHIPK3-bta-miR-499- ADAMTS6 regulatory network. • TCONS00024465 and circHIPK3 competitively bind bta-miR-499, thereby targeting ADAMTS6. • ADAMTS6 regulates skeletal muscle development by inhibiting myoblast proliferation and promoting myoblast differentiation. • New insights into the molecular basis of cattle-yak muscle development. [ABSTRACT FROM AUTHOR]