Characterization of RNA Editome in the Mammary Gland of Yaks during the Lactation and Dry Periods

SIMPLE SUMMARY: In order to study the influence of RNA editing sites on lactation and mammary gland development process in yaks, we comprehensively characterized the RNA editome of the yak mammary gland during the lactation period and dry period by using the transcriptome and genome sequencing data. The results revealed 82,872 nonredundant RNA editing sites, 14,159 of which were differentially edited between the lactation period and dry period. Enrichment analysis showed that the genes harboring differential editing sites were mainly associated with mammary gland development-related pathways, such as MAPK pathway, PI3K-Akt pathway, FoxO signaling pathway, GnRH signaling pathway, and focal adhesion pathway. Our findings offer some novel insights into the RNA editing function in the mammary gland of yaks. ABSTRACT: The mammary gland is a complicated organ comprising several types of cells, and it undergoes extensive morphogenetic and metabolic changes during the female reproductive cycle. RNA editing is a posttranscriptional modification event occurring at the RNA nucleotide level, and it drives transcriptomic and proteomic diversities, with potential functional consequences. RNA editing in the mammary gland of yaks, however, remains poorly understood. Here, we used REDItools to identify RNA editing sites in mammary gland tissues in yaks during the lactation period (LP, n = 2) and dry period (DP, n = 3). Totally, 82,872 unique RNA editing sites were identified, most of which were detected in the noncoding regions with a low editing degree. In the coding regions (CDS), we detected 5235 editing sites, among which 1884 caused nonsynonymous amino acid changes. Of these RNA editing sites, 486 were found to generate novel possible miRNA target sites or interfere with the initial miRNA binding sites, indicating that RNA editing was related to gene regulation mediated by miRNA. A total of 14,159 RNA editing sites (involving 3238 common genes) showed a significant differential editing level in the LP when compared with that in the DP through Tukey’s Honest Significant Difference method (p < 0.05). According to the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, genes that showed different RNA editing levels mainly participated in pathways highly related to mammary gland development, including MAPK, PI3K-Akt, FoxO, and GnRH signaling pathways. Collectively, this work demonstrated for the first time the dynamic RNA editome profiles in the mammary gland of yaks and shed more light on the mechanism that regulates lactation together with mammary gland development.