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Whole Genome Expression Differences in Human Left and Right Atria Ascertained by RNA Sequencing

Background— The left and right atria have different susceptibilities toward developing arrhythmias, with left atrial arrhythmias more commonly observed. To understand the molecular basis for such differences, we catalogued micro (mi)RNA and mRNA expression differences by next generation sequencing. Methods and Results— Four human left-right atrial pairs were subjected to whole-genome expression analyses via next-generation sequencing of small RNAs, including miRNAs, and poly-A–enriched mRNAs. Using a paired sample design, significant differences in the expression of 32 miRNAs were found in between the left and right atria at a probability value of <0.01. Hsa-miR-143 was the most highly expressed miRNA in the atria, as quantified by RNA sequencing. There were 746 and 2292 differentially expressed mRNAs between the left and right atria at false discovery rates of <0.001 and <0.05, respectively. Transcription factor binding elements within 2 kb of RefSeq genes were determined and specific motifs were identified that were enriched in differentially expressed genes. Similarly, specific miRNA target sequences in 3′ UTRs were also enriched in differentially expressed genes. In addition, 11 novel noncoding RNAs of unknown function were found to be differentially expressed between the left and right atria. Conclusions— There are significant differences in miRNA and mRNA expression profiles between the left and right atria, which may yield insight into increased the arrhythmogenesis of the left atria.