Integrated Small RNA Sequencing, Transcriptome, and GWAS Data Reveal miRNA Regulation in Response to Milk Protein Traits in Chinese Holstein Cattle

Abstract Background: Milk protein is one of the most important economic traits in the milk industry. Our previous study has revealed some functional genes responsible for milk protein synthesis in mammals. Yet, the miRNA-mediated gene regulatory network for the synthesis of milk protein in mammary is poorly understood. Results: 12 samples from Chinese Holstein Cows with three too high and three low phenotypic values for milk protein percentage in lactation and non-lactating were examined through deep small RNA sequencing. By bioinformatics analysis, we characterized 387 known and 212 novel miRNAs in the mammary gland. Differentially expressed analysis detected 28 miRNAs in lactation and 52 miRNAs in the non-lactating period with a highly significant correlation with milk protein concentration. Target prediction and correlation analysis identified some key miRNAs and their targets potentially involved in the synthesis of milk protein. Using genome-wide association signal (GWAS) enrichment analysis among five milk production traits, we found the differentially expressed targets were significantly related to milk protein traits.Conclusions: This integrated study on the transcriptional and post-transcriptional regulatory profiles between significantly differential phenotype of milk protein concentration provides new insights into the mechanism of milk protein synthesis, which should reveal the regulatory mechanisms of milk secretion.