miRNA-dependent gene silencing involving Ago2-mediated cleavage of a circular antisense RNA
miRNA-dependent gene silencing involving Ago2-mediated cleavage of a circular antisense RNA
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DOI：
10.1038/emboj.2011.359
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发表时间：
2011-11-02
期刊：
影响因子：
11.4
通讯作者：
Kjems, Jorgen
中科院分区：
文献类型：
--
作者：
Hansen, Thomas B.;Wiklund, Erik D.;Kjems, Jorgen
微小RNA（miRNA）类似于22 nt非编码RNA，其通常结合细胞质中靶mRNA的3' UTR，导致mRNA不稳定和翻译抑制。在这里，我们报告说，miRNA也可以通过靶向人类细胞中的非编码反义转录物来调节基因表达。具体来说，我们表明，miR-671指导切割的小脑变性相关蛋白1（CDR 1）基因座的环状反义转录物在Ago 2切片依赖性的方式。所产生的环状反义下调伴随着CDR 1 mRNA水平的降低，与异染色质形成无关。这项研究提供了第一个证据，非编码反义转录作为功能性miRNA的目标，和一个新的调控机制，涉及mRNA和反义环状RNA水平之间的正相关性。The EMBO Journal（2011）30，4414-4422. doi：10.1038/doj.2011.359; 2011年9月30日在线发布
MicroRNAs (miRNAs) are similar to 22 nt non-coding RNAs that typically bind to the 3' UTR of target mRNAs in the cytoplasm, resulting in mRNA destabilization and translational repression. Here, we report that miRNAs can also regulate gene expression by targeting non-coding antisense transcripts in human cells. Specifically, we show that miR-671 directs cleavage of a circular antisense transcript of the Cerebellar Degeneration-Related protein 1 (CDR1) locus in an Ago2-slicer-dependent manner. The resulting downregulation of circular antisense has a concomitant decrease in CDR1 mRNA levels, independently of heterochromatin formation. This study provides the first evidence for non-coding antisense transcripts as functional miRNA targets, and a novel regulatory mechanism involving a positive correlation between mRNA and antisense circular RNA levels. The EMBO Journal (2011) 30, 4414-4422. doi:10.1038/emboj.2011.359; Published online 30 September 2011