Functional sequestration of microRNA-122 from Hepatitis C Virus by circular RNA sponges

RNA Biol. 2018;15(8):1032-1039. doi: 10.1080/15476286.2018.1435248. Epub 2018 Feb 28.

Abstract

Circular RNAs (circRNAs) were recently described as a novel class of cellular RNAs. Two circRNAs were reported to function as molecular sponges, sequestering specific microRNAs, thereby de-repressing target mRNAs. Due to their elevated stability in comparison to linear RNA, circRNAs may be an interesting tool in molecular medicine and biology. In this study, we provide a proof-of-principle that circRNAs can be engineered as microRNA sponges. As a model system, we used the Hepatitis C Virus (HCV), which requires cellular microRNA-122 for its life cycle. We produced artificial circRNA sponges in vitro that efficiently sequester microRNA-122, thereby inhibiting viral protein production in an HCV cell culture system. These circRNAs are more stable than their linear counterparts, and localize both to the cytoplasm and to the nucleus, opening up a wide range of potential applications.

Keywords: Circular RNA; Hepatitis C Virus; RNA therapy; microRNA-122; molecular sponge.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / virology
  • Hepacivirus / genetics*
  • Hepacivirus / isolation & purification
  • Hepatitis C / genetics*
  • Hepatitis C / pathology
  • Hepatitis C / virology
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Liver Neoplasms / virology
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • RNA / genetics*
  • RNA, Circular
  • Tumor Cells, Cultured

Substances

  • MIRN122 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • RNA

Grant support

This work was funded by the LOEWE program Medical RNomics (State of Hessen; to NM, AB, OR) and the SFB 1021 (DFG; to MN).