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000305776 1001_ $$00000-0001-7201-6341$$aGlaich, Ohad$$b0
000305776 245__ $$aDNA methylation directs microRNA biogenesis in mammalian cells.
000305776 260__ $$a[London]$$bSpringer Nature$$c2019
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000305776 520__ $$aMicroRNA (miRNA) biogenesis initiates co-transcriptionally, but how the Microprocessor machinery pinpoints the locations of short precursor miRNA sequences within long flanking regions of the transcript is not known. Here we show that miRNA biogenesis depends on DNA methylation. When the regions flanking the miRNA coding sequence are highly methylated, the miRNAs are more highly expressed, have greater sequence conservation, and are more likely to drive cancer-related phenotypes than miRNAs encoded by unmethylated loci. We show that the removal of DNA methylation from miRNA loci leads to their downregulation. Further, we found that MeCP2 binding to methylated miRNA loci halts RNA polymerase II elongation, leading to enhanced processing of the primary miRNA by Drosha. Taken together, our data reveal that DNA methylation directly affects miRNA biogenesis.
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000305776 650_7 $$2NLM Chemicals$$aMethyl-CpG-Binding Protein 2
000305776 650_7 $$2NLM Chemicals$$aMicroRNAs
000305776 650_2 $$2MeSH$$aAnimals
000305776 650_2 $$2MeSH$$aCell Line
000305776 650_2 $$2MeSH$$aDNA Methylation
000305776 650_2 $$2MeSH$$aHumans
000305776 650_2 $$2MeSH$$aMethyl-CpG-Binding Protein 2: genetics
000305776 650_2 $$2MeSH$$aMethyl-CpG-Binding Protein 2: metabolism
000305776 650_2 $$2MeSH$$aMice
000305776 650_2 $$2MeSH$$aMicroRNAs: genetics
000305776 650_2 $$2MeSH$$aMicroRNAs: metabolism
000305776 650_2 $$2MeSH$$aOpen Reading Frames
000305776 650_2 $$2MeSH$$aRNA Processing, Post-Transcriptional
000305776 7001_ $$00000-0001-6364-9307$$aParikh, Shivang$$b1
000305776 7001_ $$aBell, Rachel E$$b2
000305776 7001_ $$aMekahel, Keren$$b3
000305776 7001_ $$aDonyo, Maya$$b4
000305776 7001_ $$aLeader, Yodfat$$b5
000305776 7001_ $$aShayevitch, Ronna$$b6
000305776 7001_ $$aSheinboim, Danna$$b7
000305776 7001_ $$aYannai, Sivan$$b8
000305776 7001_ $$aHollander, Dror$$b9
000305776 7001_ $$aMelamed, Ze'ev$$b10
000305776 7001_ $$aLev-Maor, Galit$$b11
000305776 7001_ $$aAst, Gil$$b12
000305776 7001_ $$aLevy, Carmit$$b13
000305776 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-019-13527-1$$gVol. 10, no. 1, p. 5657$$n1$$p5657$$tNature Communications$$v10$$x2041-1723$$y2019
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