A map of human circular RNAs in clinically relevant tissues

Abstract

Cellular circular RNAs (circRNAs) are generated by head-to-tail splicing and are present in all multicellular organisms studied so far. Recently, circRNAs have emerged as a large class of RNA which can function as post-transcriptional regulators. It has also been shown that many circRNAs are tissue- and stage-specifically expressed. Moreover, the unusual stability and expression specificity make circRNAs important candidates for clinical biomarker research. Here, we present a circRNA expression resource of 20 human tissues highly relevant to disease-related research: vascular smooth muscle cells (VSMCs), human umbilical vein cells (HUVECs), artery endothelial cells (HUAECs), atrium, vena cava, neutrophils, platelets, cerebral cortex, placenta, and samples from mesenchymal stem cell differentiation. In eight different samples from a single donor, we found highly tissue-specific circRNA expression. Circular-to-linear RNA ratios revealed that many circRNAs were expressed higher than their linear host transcripts. Among the 71 validated circRNAs, we noticed potential biomarkers. In adenosine deaminase-deficient, severe combined immunodeficiency (ADA-SCID) patients and in Wiskott-Aldrich-Syndrome (WAS) patients’ samples, we found evidence for differential circRNA expression of genes that are involved in the molecular pathogenesis of both phenotypes. Our findings underscore the need to assess circRNAs in mechanisms of human disease.Key messages circRNA resource catalog of 20 clinically relevant tissues.circRNA expression is highly tissue-specific.circRNA transcripts are often more abundant than their linear host RNAs.circRNAs can be differentially expressed in disease-associated genes. Electronic supplementary materialThe online version of this article (10.1007/s00109-017-1582-9) contains supplementary material, which is available to authorized users.

Selective release of circRNAs in platelet‐derived extracellular vesicles

“…As shown in this work and by others [20,35], circRNAs are clearly enriched in platelets compared to other blood cells. Moreover, the ratio between the linear spliced mRNA and the circular isoform is very often shifted towards the circular form, which is more stable than linear RNA [20].…”

Circular RNA circNOL10 Inhibits Lung Cancer Development by Promoting SCLM1‐Mediated Transcriptional Regulation of the Humanin Polypeptide Family

“…However, related studies have mainly concentrated on DNA methylation and histone modification, [2][3][4] and the roles of noncoding RNAs in lung cancer remain uncertain. [10][11][12][13] However, the functions of most of the thousands of unique circRNAs discovered to date remain unknown. [5][6][7] Increasing numbers of types of noncoding RNAs with different functions have been identified in recent studies, and circular RNAs (circRNAs), which represent a new type of noncoding RNAs, have become a recent topic of research.…”

Current status and potential role of circular RNAs in neurological disorders

“…CircRNAs are widely distributed in various organ systems such as the heart, brain, liver, lung, kidney, skin, and blood, and their expression is typically tissue‐ and development‐specific (Memczak et al ; Szabo et al ; Xia et al ; Maass et al ; Zhou et al ; Zaghlool et al ). In particular, circRNAs are highly enriched in neuronal tissues (Westholm et al ; Rybak‐Wolf et al ; You et al ).…”