A map of human circular RNAs in clinically relevant tissues

Philipp G. Maass*, Petar Glažar, Sebastian Memczak, Gunnar Dittmar, Irene Hollfinger, Luisa Schreyer, Aisha V. Sauer, Okan Toka, Alessandro Aiuti, Friedrich C. Luft, Nikolaus Rajewsky

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

262 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1179-1189
Number of pages11
JournalJournal of Molecular Medicine
Volume95
Issue number11
DOIs
Publication statusPublished - 1 Nov 2017
Externally publishedYes

Keywords

  • Circular RNAs
  • Human cell types
  • Potential biomarker
  • circRNA catalog

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