miRNA 依赖的基因沉默涉及 Ago2 介导的环状反义 RNA 的切割。
miRNA-dependent gene silencing involving Ago2-mediated cleavage of a circular antisense RNA.
机构信息
Department of Molecular Biology, Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus, Denmark.
出版信息
EMBO J. 2011 Sep 30;30(21):4414-22. doi: 10.1038/emboj.2011.359.
Abstract
MicroRNAs (miRNAs) are ∼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.
摘要
微小 RNA（miRNA）是约 22 个核苷酸的非编码 RNA，通常在细胞质中与靶 mRNA 的 3'UTR 结合，导致 mRNA 不稳定性和翻译抑制。在这里，我们报告说 miRNA 还可以通过靶向人类细胞中非编码反义转录本来调节基因表达。具体来说，我们表明 miR-671 以 Ago2-slicer 依赖性方式指导小脑退化相关蛋白 1（CDR1）基因座的环状反义转录本的切割。由此导致的环状反义的下调与 CDR1 mRNA 水平的相应降低相关，而与异染色质形成无关。这项研究首次为非编码反义转录本作为功能性 miRNA 靶标提供了证据，并提供了一种新的调控机制，涉及 mRNA 和反义环状 RNA 水平之间的正相关关系。
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