Background Staphylococcus aureus (S. aureus) mastitis is one of the most difficult diseases to treat in lactating dairy cows worldwide. S. aureus with different lineages leads to different host immune responses. Long non-coding RNAs (lncRNAs) are reported to be widely involved in the progress of inflammation. However, no research has identified stable lncRNAs among different S. aureus strain infections. In addition, folic acid (FA) can effectively reduce inflammation, and whether the inflammatory response caused by S. aureus can be reduced by FA remains to be explored. Methods lncRNA transcripts were identified from Holstein mammary gland tissues infected with different concentrations of S. aureus (in vivo) and mammary alveolar cells (Mac-T cells, in vitro) challenged with different S. aureus strains. Differentially expressed (DE) lncRNAs were evaluated, and stable DE lncRNAs were identified in vivo and in vitro. On the basis of the gene sequence conservation and function conservation across species, key lncRNAs with the function of potentially immune regulation were retained for further analysis. The function of FA on inflammation induced by S. aureus challenge was also investigated. Then, the association analysis between these keys lncRNA transcripts and hematological parameters (HPs) was carried out. Lastly, the knockdown and overexpression of the important lncRNA were performed to validate the gene function on the regulation of cell immune response. Results Linear regression analysis showed a significant correlation between the expression levels of lncRNA shared by mammary tissue and Mac-T cells (P < 0.001, R2 = 0.3517). lncRNAs PRANCR and TNK2–AS1 could be regarded as stable markers associated with bovine S. aureus mastitis. Several HPs could be influenced by SNPs around lncRNAs PRANCR and TNK2–AS1. The results of gene function validation showed PRANCR regulates the mRNA expression of SELPLG and ITGB2 within the S. aureus infection pathway and the Mac-T cells apoptosis. In addition, FA regulated the expression change of DE lncRNA involved in toxin metabolism and inflammation to fight against S. aureus infection. Conclusions The remarkable association between SNPs around these two lncRNAs and partial HP indicates the potentially important role of PRANCR and TNK2–AS1 in immune regulation. Stable DE lncRNAs PRANCR and TNK2–AS1 can be regarded as potential targets for the prevention of bovine S. aureus mastitis. FA supplementation can reduce the negative effect of S. aureus challenge by regulating the expression of lncRNAs.

The present study was designed to evaluate the association of polymorphisms in bovine trafficking protein particle complex subunit 9 (TRAPPC9) and cluster of differentiation 4 (CD4) genes with milk production and mastitis resistance phenotypic traits in a different cattle population. Three single nucleotide polymorphisms (SNPs) (SNP1 Position: Chr14:2484891, SNP2 (rs110017379), SNP3 Position: Chr14:2525852) in bovine TRAPPC9 and one SNP (Position: Chr5:104010752) in CD4 were screened through Chinese Cow's SNPs Chip-I (CCSC-I) and genotyped in a population of 312 Chinese Holsteins (156: Mastitis, 156: Healthy). The results were analyzed using the general linear model in SAS 9.4. Our analysis revealed that milk protein percentage, somatic cell count (SCC), somatic cell score (SCS), serum cytokines interleukin 6 (IL-6) and interferon-gamma (IFN-γ) were significantly (P &lt; 0.05) associated with at least one or more identified SNPs of TRAPPC9 and CD4 genes. Furthermore, the expression status of SNPs in CD4 and TRAPPC9 genes were verified through RT-qPCR. The expression analysis showed that genotypes GG in SNP3 of TRAPPC9 and TT genotype in SNP4 of CD4 showed higher expression level compared to other genotypes. The GG genotype in SNP2 and TT genotype in SNP3 of TRAPPC9 were associated with higher bovine milk SCC and lower IL6. Altogether, our findings suggested that the SNPs of TRAPPC9 and CD4 genes could be useful genetic markers in selection for milk protein improvement and mastitis resistance phenotypic traits in dairy cattle. The CCSC-I used in current study is proposed to be validate in different and large population of dairy cattle not only in China but also in other countries. Moreover, our analyses recommended that besides SCC and SCS, the association of genetic markers could also be considered with the serum cytokines (IL-6, IFN-γ) while selecting genetically mastitis resistance dairy cattle.

N 6-methyladenosine (m 6A) is the most functionally important epigenetic modification in RNA. The m 6A modification widely exists in mRNA and noncoding RNA, influences the mRNA processing, and regulates the secondary structure and maturation of noncoding RNA. Studies showed the important regulatory roles of m 6A modification in animal’s complex traits, such as development, immunity, and reproduction-related traits. As an important intermediate stage from animal genome to phenotype, the function of m 6A in the complex trait formation of domestic animals cannot be neglected. This review discusses recent research advances on m 6A modification in well-studied organisms, such as human and model organisms, and introduces m 6A detection technologies, small-molecule inhibitors of m 6A-related enzymes, interaction between m 6A and other biological progresses, and the regulation mechanisms of m 6A in domesticated animals’ complex traits.