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

RNA Biology
Isabelle JostO Rossbach

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.

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Methods Mentioned

BETA
in vitro transcription
pulldown
PCR
transfections
antisense oligonucleotide
electrophoresis
gel filtration
transfection

Software Mentioned

ImageQuantTL
OriginPro8

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