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Cell Res. 2012 Mar;22(3):504-15. doi: 10.1038/cr.2011.137. Epub 2011 Aug 23.

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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Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing Jiangsu 210093, China.


MicroRNAs (miRNAs) are endogenous noncoding RNAs (∼22 nt) that regulate target gene expression at the post-transcriptional 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.

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