Mouse miRNA-709 directly regulates miRNA-15a/16-1 biogenesis at the posttranscriptional level in the nucleus: evidence for a microRNA hierarchy system
Mouse miRNA-709 directly regulates miRNA-15a/16-1 biogenesis at the posttranscriptional level in the nucleus: evidence for a microRNA hierarchy system
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DOI：
10.1038/cr.2011.137
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发表时间：
2012-03-01
期刊：
影响因子：
44.1
通讯作者：
Zen, Ke
中科院分区：
文献类型：
--
作者：
Tang, Rui;Li, Limin;Zen, Ke
microRNA（miRNAs）是一类内源性非编码RNA（类似于22 nt），在细胞质中在转录后水平调控靶基因的表达。最近发现的miRNA和miRNA功能所需的argonaute家族蛋白在细胞核中的存在促使我们假设，miRNA也可能在细胞核中具有调节功能。在这项研究中，我们证明了小鼠miR-709主要位于各种细胞类型的细胞核中，并且其核定位模式在凋亡刺激后迅速变化。在细胞核中，miR-709直接与pri-miR-15 a/16-1上的19-nt miR-709识别元件结合，并阻止其加工成pre-miR-15 a/16-1，导致miR-15 a/16-1成熟的抑制。此外，核miR-709通过miR-15 a/16-1途径参与细胞凋亡的调节。总之，本研究提供了第一个证据，证明一种miRNA可以通过直接靶向细胞核中的初级转录本来控制其他miRNA的生物合成。
MicroRNAs (miRNAs) are endogenous noncoding RNAs (similar to 22 nt) that regulate target gene expression at the posttranscriptional level in the cytoplasm. Recent discoveries of the presence of miRNAs and miRNA function-required argonaute family proteins in the cell nucleus have prompted us to hypothesize that miRNAs may also have regulatory functions in the cell nucleus. In this study, we demonstrate that mouse miR-709 is predominantly located in the nucleus of various cell types and that its nuclear localization pattern rapidly changes upon apoptotic stimuli. In the cell nucleus, miR-709 directly binds to a 19-nt miR-709 recognition element on pri-miR-15a/16-1 and prevents its processing into pre-miR-15a/16-1, leading to a suppression of miR-15a/16-1 maturation. Furthermore, nuclear miR-709 participates in the regulation of cell apoptosis through the miR-15a/16-1 pathway. In summary, the present study provides the first evidence that one miRNA can control the biogenesis of other miRNAs by directly targeting their primary transcripts in the nucleus.