Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
Sci Rep. 2018 Nov 16;8(1):16953. doi: 10.1038/s41598-018-35001-6.
Circular RNAs (circRNAs) were recently discovered as a class of widely expressed noncoding RNA and have been implicated in regulation of gene expression. However, the function of the majority of circRNAs remains unknown. Studies of circRNAs have been hampered by a lack of essential approaches for detection, quantification and visualization. We therefore developed a target-enrichment sequencing method suitable for screening of circRNAs and their linear counterparts in large number of samples. We also applied padlock probes and in situ sequencing to visualize and determine circRNA localization in human brain tissue at subcellular levels. We measured circRNA abundance across different human samples and tissues. Our results highlight the potential of this RNA class to act as a specific diagnostic marker in blood and serum, by detection of circRNAs from genes exclusively expressed in the brain. The powerful and scalable tools we present will enable studies of circRNA function and facilitate screening of circRNA as diagnostic biomarkers.
环状 RNA（circRNAs）最近被发现为一类广泛表达的非编码 RNA，并被认为参与了基因表达的调控。然而，大多数 circRNAs 的功能仍然未知。circRNAs 的研究受到缺乏用于检测、定量和可视化的基本方法的阻碍。因此，我们开发了一种适合于在大量样本中筛选 circRNAs 及其线性对应物的目标富集测序方法。我们还应用了锁式探针和原位测序来在亚细胞水平上可视化和确定人脑组织中 circRNA 的定位。我们测量了不同人类样本和组织中的 circRNA 丰度。我们的结果强调了这类 RNA 作为血液和血清中特定诊断标记物的潜力，通过检测仅在大脑中表达的基因的 circRNAs。我们提出的强大和可扩展的工具将能够研究 circRNA 的功能，并促进作为诊断生物标志物的 circRNA 的筛选。
