Identification and characterization of circular RNAs as a new class of putative biomarkers in human blood

Covalently closed circular RNA molecules (circRNAs) have recently emerged as a class of RNA isoforms with widespread and tissue specific expression across animals, oftentimes independent of the corresponding linear mRNAs. circRNAs are remarkably stable and sometimes highly expressed molecules. Here, we sequenced RNA in human peripheral whole blood to determine the potential of circRNAs as biomarkers in an easily accessible body fluid. We report the reproducible detection of thousands of circRNAs. Importantly, we observed that hundreds of circRNAs are much higher expressed than corresponding linear mRNAs. Thus, circRNA expression in human blood reveals and quantifies the activity of hundreds of coding genes not accessible by classical mRNA specific assays. Our findings suggest that circRNAs could be used as biomarker molecules in standard clinical blood samples. Sequencing of blood RNA from five healthy individuals (biological replicates) plus technical replicate of one sample and detection of circRNAs.共价闭合环状RNA分子（circRNAs）近年来被认定为一类RNA异构体，在动物界中广泛表达且具有组织特异性，其表达通常独立于对应的线性mRNA。环状RNA稳定性极强，且部分可实现高丰度表达。本研究通过对人类外周全血中的RNA进行测序，以探究环状RNA作为易于获取的体液中的生物标志物的潜力。本研究成功重复检测到数千种环状RNA。尤为重要的是，本研究发现数百种环状RNA的表达丰度远高于对应的线性mRNA。因此，对人类血液中环状RNA表达的检测，可以揭示并定量数百种无法通过经典mRNA特异性检测方法获取的编码基因的活性。本研究结果表明，环状RNA可作为标准临床血液样本中的生物标志物分子。实验包含对5名健康个体（生物学重复）的血液RNA进行测序，同时对1份样本设置技术重复，并完成环状RNA的检测。