Whole genome expression differences in human left and right atria ascertained by RNA sequencing.
Whole genome expression differences in human left and right atria ascertained by RNA sequencing.
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DOI：
10.1161/circgenetics.111.961631
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发表时间：
2012-06
期刊：
影响因子：
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通讯作者：
Smith JD
中科院分区：
文献类型：
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作者：
Hsu J;Hanna P;Van Wagoner DR;Barnard J;Serre D;Chung MK;Smith JD
左心房和右心房对发生心律失常具有不同的易感性，左房性心律失常更常见。为了理解这种差异的分子基础，我们通过下一代测序对miRNA和mRNA表达差异进行了编目。通过下一代小RNA测序对四对人左-右心房进行全基因组表达分析，所述小RNA包括微RNA（miRNA）和富含多聚腺苷酸的mRNA。使用配对样本设计，在左心房和右心房之间发现32种miRNA表达的显著差异，p值<0.01。Hsa-miR-143是心房中最高表达的miRNA，如通过RNA-seq定量的。左心房和右心房之间分别有746和2292个差异表达的mRNA，错误发现率分别为<0.001和<0.05。确定RefSeq基因的2kb内的转录因子结合元件，并鉴定在差异表达基因中富集的特异性基序。类似地，3'UTR中的特异性miRNA靶序列也在差异表达基因中富集。此外，还发现了11种功能未知的新型非编码RNA在左心房和右心房之间差异表达。左心房和右心房之间的miRNA和mRNA表达谱存在显著差异，这可能有助于了解左心房的心肌发生增加。
The left and right atria have different susceptibilities towards developing arrhythmias, with left atrial arrhythmias more commonly observed. To understand the molecular basis for such differences, we catalogued miRNA and mRNA expression differences by next generation sequencing. Four human left-right atrial pairs were subjected to whole-genome expression analyses via next generation sequencing of small RNAs, including microRNAs (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 p-value of <0.01. Hsa-miR-143 was the most highly expressed miRNA in the atria, as quantified by RNA-seq. 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 eleven novel non-coding RNAs of unknown function were found to be differentially expressed between the left and right atria. 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.