ABSTRACT: Purpose: The goal of this study was to reveal epigenetic differences in the microRNA transcriptomes of two organs (heart and lung) between yak and cattle. Methods: Three unrelated 2-year old adult females for both of yaks and cattle (Luxi Huang cattle) were used in this study. Two of significant hypoxia-responsive tissues (heart and lung) were rapidly collected from each carcass, washed three times with physiological saline, immediately frozen in liquid nitrogen. All frozen samples were stored at –80 °C until RNA extraction.The total RNA were extracted with Trizol (Ambion, USA). NanoDrop ND-2000 spectrophotometer (Nano Drop, DE, USA) and Bioanalyzer 2100 (Agilent Technologies, Santa Clara, CA, USA) were used to monitor the concentration and integrity of RNA, respectively. In brief, several successive steps consist the Illumina sequencing. The small RNA with length of 14-40 nt were first purified by polyacrylamide gel electrophoresis (PAGE), and then specific adapters were ligated to the purified small RNA. The ligated RNA were reverse transcribed to cDNA libraries. Finally, each library were sequenced on Genome Analyzer. Results: We identified 808 widely-expressed conserved and 697 species-specific novel miRNAs in two species. In addition, although two organs showed similar high expression miRNAs, larger differentiation was present in lung than heart between two species. In addition, miRNAs with significantly differentiated patterns of expression in two organs exhibited obvious co-operation effect in high altitude adaptation in form of miRNA family and cluster. Functional analysis revealed that a large amount of differentially expressed miRNAs were enriched in hypoxia-related pathways, such as VEGF signaling pathway, HIF-1α signaling pathway, insulin signaling pathway, DNA damage response, apoptosis, fatty acid metabolism and glucose metabolism. These results suggested the diverse degrees of epigenetic variation in different tissues between yak and cattle, and revealed extensive roles of miRNAs in high altitude adaptation. Conclusions: In this study, we illustrated the differences in the microRNA transcriptomes level for heart and lung between yak and cattle, and suggested extensive roles of miRNAs in high altitude adaptation. The work performed here will provide a typical demonstration for future deciphering the mechanism of high altitude adaptation
