Abstract
MicroRNAs (miRNAs or miRs) are small regulatory RNAs crucial for modulation of signaling pathways in multiple organs. While the link between miRNAs and heart disease has grown more readily apparent over the past three years, these data are primarily limited to small animal models or cell-based systems. Here, we performed a high-throughput RNA sequencing (RNAseq) analysis of left ventricle and other tissue from a pre-clinical ovine model. We identified 172 novel miRNA precursors encoding a total of 264 mature miRNAs. Notably, 84 precursors were detected in both the left ventricle and other tissues. However, 10 precursors, encoding 11 mature sequences, were specific to the left ventricle. Moreover, the total 168 novel miRNA precursors included 22 non-conserved ovine-specific sequences. Our data identify and characterize novel miRNAs in the left ventricle of sheep, providing fundamental new information for our understanding of protein regulation in heart and other tissues.
Highlights
Coronary artery disease is the most common cause for mortality and development of heart failure in the United States [1,2,3,4]
To detect novel left ventricle specific miRNAs, a second small-RNA library (LV, “Left Ventricle specific” library) was generated from RNA samples obtained from the left ventricle of three adult male Dorset sheep
Illumina sequencing of the purified cDNA libraries generated 21,343,067 total raw reads: 9,512,054 from the left ventricular (LV) library and 11,831,013 from the global library
Summary
Coronary artery disease is the most common cause for mortality and development of heart failure in the United States [1,2,3,4]. Large animal models have been developed to study myocardial infarction with resultant ischemic heart failure [5,6,7,8,9,10,11,12]. The molecular mechanisms underlying development of heart failure in this critical pre-clinical model are unknown. MiRNAs are small non-coding RNAs that act as post-transcriptional regulators of gene expression [14,15]. Their mature form (ffi18Ä22 nt long) is incorporated into a protein complex called RISC (RNA-induced silencing complex) to which they confer binding specificity to target mRNA molecules. Their mature form (ffi18Ä22 nt long) is incorporated into a protein complex called RISC (RNA-induced silencing complex) to which they confer binding specificity to target mRNA molecules. miRNAs can bind their targets through partial or perfect
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