Potent degradation of neuronal miRNAs induced by highly complementary targets
Potent degradation of neuronal miRNAs induced by highly complementary targets
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DOI：
10.15252/embr.201540078
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发表时间：
2015-04-01
期刊：
影响因子：
7.7
通讯作者：
Grosshans, Helge
中科院分区：
文献类型：
--
作者：
de la Mata, Manuel;Gaidatzis, Dimos;Grosshans, Helge
microRNA（miRNAs）通过沉默靶mRNA来调节靶mRNA。然而，反过来，靶mRNA也可以调节miRNA稳定性。在这里，我们揭示了靶RNA指导的miRNA降解（TDMD）在啮齿动物原代神经元中的显着功效。与降解一致，并且尽管仍与Argonaute结合，但靶向的miRNA是3'末端加尾和修剪的。对miRNA及其衰变诱导靶点的绝对定量表明，神经元TDMD是多次转换，不涉及靶点的共降解，而是与miRNA介导的靶点衰变竞争。此外，mRNA沉默（而不是TDMD）依赖于多个靶位点之间的协同作用来达到高功效。这一知识可以用于有效去除丰富的miRNA。我们的研究结果使我们深入了解了原代神经元中一种有效的miRNA降解途径，其TDMD活性大大超过了非神经元细胞和已建立的细胞系。因此，TDMD可能与神经系统中的miRNA调控特别相关。
MicroRNAs (miRNAs) regulate target mRNAs by silencing them. Reciprocally, however, target mRNAs can also modulate miRNA stability. Here, we uncover a remarkable efficacy of target RNA-directed miRNA degradation (TDMD) in rodent primary neurons. Coincident with degradation, and while still bound to Argonaute, targeted miRNAs are 3' terminally tailed and trimmed. Absolute quantification of both miRNAs and their decay-inducing targets suggests that neuronal TDMD is multiple turnover and does not involve co-degradation of the target but rather competes with miRNA-mediated decay of the target. Moreover, mRNA silencing, but not TDMD, relies on cooperativity among multiple target sites to reach high efficacy. This knowledge can be harnessed for effective depletion of abundant miRNAs. Our findings bring insight into a potent miRNA degradation pathway in primary neurons, whose TDMD activity greatly surpasses that of non-neuronal cells and established cell lines. Thus, TDMD may be particularly relevant for miRNA regulation in the nervous system.