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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]

Yaks (Bos grunniens) are a critical livestock breed in the plateau region, and changing the feeding system of yaks can significantly improve their growth performance. The effects of different feeding regimes on the growth performance and meat quality of yaks were comprehensively compared here. The transcriptome and proteome of the Longissimus dorsi muscle were determined using RNA-seq and Tandem Mass Tag (TMT) techniques. Indoor feeding significantly improved the growth performance (such as the average daily gain and carcass weight) and meat quality characteristics compared with traditional grazing feeding. In the grazing (Group G) vs. in-house fed group (Group HF) comparison, 40 differentially expressed genes/differentially abundant proteins exhibited the same mRNA and protein expression trends. These genes were associated with collagen binding, the lipoxygenase pathway, and the arachidonic acid metabolic process. Parallel reaction monitoring verified whether the TMT results were reliable. Moreover, some pathways, such as the AMPK signaling pathway, FoxO signaling pathway, PPAR signaling pathway, and fatty acid metabolism, were significantly enriched. These results expand our knowledge about meat quality in yaks and provide practical information and more evidence for further insight into the biological mechanisms underlying meat quality traits. [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]

Cattle-yak, as the hybrid offspring of cattle (Bos taurus) and yak (Bos grunniens), demonstrates obvious heterosis in production performance. Male hybrid sterility has been focused on for a long time; however, the mRNAs and non-coding RNAs related to muscle development as well as their regulatory networks remain unclear. The phenotypic data showed that the production performance (i.e., body weight, withers height, body length, and chest girth) of cattle-yak was significantly better than that of the yak, and the economic benefits of the cattle-yak were higher under the same feeding conditions. Then, we detected the expression profiles of the longissimus dorsi muscle of cattle-yak and yak to systematically reveal the molecular basis using the high-throughput sequencing technology. Here, 7,126 mRNAs, 791 lncRNAs, and 1,057 circRNAs were identified to be differentially expressed between cattle-yaks and yaks in the longissimus dorsi muscle. These mRNAs, lncRNA targeted genes, and circRNA host genes were significantly enriched in myoblast differentiation and some signaling pathways related to muscle development (such as HIF-1 signaling pathway and PI3K-Akt signaling pathway). We constructed a competing endogenous RNA (ceRNA) network and found that some non-coding RNAs differentially expressed may be involved in the regulation of muscle traits. Taken together, this study may be used as a reference tool to provide the molecular basis for studying muscle development. [ABSTRACT FROM AUTHOR]

Domestic yak (Bos grunniens) is the most crucial livestock in the Qinghai-Tibetan Plateau, providing meat and other necessities for local people. The skeletal muscle of adult livestock is composed of muscle fibers, and fiber composition in muscle has influence on meat qualities, such as tenderness, pH, and color. Real-time quantitative polymerase chain reaction (RT-qPCR) is a powerful tool to evaluate the gene expression of muscle fiber, but the normalization of the data depends on the stability of expressed reference genes. Unfortunately, there is no consensus for an ideal reference gene for data normalization in muscle tissues of yak. In this study, we aimed to assess the stability of 14 commonly used candidate reference genes by using five algorithms (GeNorm, NormFinder, BestKeeper, Delat Ct and Refinder). Our results suggested UXT and PRL13A were the most stable reference genes, while the most commonly used reference gene, GAPDH, was most variably expressed across different muscle tissues. We also found that the extensor digitorum lateralis (EDL), trapezius pars thoracica (TPT), and psoas major (PM) muscle had the higher content of type I muscle fibers and the lowest content of type IIB muscle fibers, while gluteobiceps (GB) muscle had the highest content of type IIB muscle fibers. Our study provides the suitable reference genes for accurate analysis of yak muscle fiber composition. [ABSTRACT FROM AUTHOR]

The energy available from the diet, which affects fat deposition in vivo, is a major factor in the expression of genes regulating fat deposition in the longissimus dorsi muscle. Providing high-energy diets to yaks might increase intramuscular fat deposition and fatty acid concentrations under a traditional grazing system in cold seasons. A total of fifteen adult castrated male yaks with an initial body weight 274.3 ± 3.14 kg were analyzed for intramuscular adipose deposition and fatty acid composition. The animals were divided into three groups and fed low-energy (LE: 5.5 MJ/kg), medium-energy (ME: 6.2 MJ/kg) and high-energy (HE: 6.9 MJ/kg) diets, respectively. All animals were fed ad libitum twice daily at 08:00–09:00 am and 17:00–18:00 pm and with free access to water for 74 days, including a 14-d period to adapt to the diets and the environment. Intramuscular fat (IMF) content, fatty acid profile and mRNA levels of genes involved in fatty acid synthesis were determined. The energy levels of the diets significantly (P<0.05) affected the content of IMF, total SFA, total MUFA and total PUFA. C16:0, C18:0 and C18:1n9c account for a large proportion of total fatty acids. Relative expression of acetyl-CoA carboxylase (ACACA), fatty acid synthase (FASN), stearoyl-CoA desaturase (SCD), sterol regulatory element-binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor γ (PPARγ) and fatty acid-binding protein 4 (FABP4) was greater in HE than in LE yaks (P<0.05). Moreover, ME yaks had higher (P<0.05) mRNA expression levels of PPARγ, ACACA, FASN, SCD and FABP4 than did the LE yaks. The results demonstrate that the higher energy level of the diets increased IMF deposition and fatty acid content as well as increased intramuscular lipogenic gene expression during the experimental period. [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]