Natural RNA circles function as efficient microRNA sponges

摘要

MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression that act by direct base pairing to target sites within untranslated regions of messenger RNAs. Recently, miRNA activity has been shown to be affected by the presence of miRNA sponge transcripts, the so-called competing endogenous RNA in humans and target mimicry in plants. We previously identified a highly expressed circular RNA (circRNA) in human and mouse brain8. Here we show that this circRNA acts as a miR-7 sponge; we term this circular transcript ciRS-7 (circular RNA sponge for miR-7). ciRS-7 contains more than 70 selectively conserved miRNA target sites, and it is highly and widely associated with Argonaute (AGO) proteins in a miR-7-dependent manner. Although the circRNA is completely resistant to miRNA-mediated target destabilization, it strongly suppresses miR-7 activity, resulting in increased levels of miR-7 targets. In the mouse brain, we observe overlapping co-expression of ciRS-7 and miR-7, particularly in neocortical and hippocampal neurons, suggesting a high degree of endogenous interaction. We further show that the testis-specific circRNA, sex-determining region Y (Sty), serves as a miR-138 sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon. This study serves as the first, to our knowledge, functional analysis of a naturally expressed circRNA.%环RNA(circRNA)已在哺乳动物细胞中被发rn现，但它们的功能一直不清楚。现在，来自rnNikolaus Rajewsky实验室和J?rgerl Kiems实验rn室的两篇论文确定了与微RNA miR-7相结合的rn一个环RNA的一种功能。他们发现，这个环rnRNA充满了微RNA结合点，可起“海绵”的作rn用，能在每个环RNA分子上结合大量微RNA。rn这些研究说明环RNA在转录后调控中扮演一个角色。