期刊
NATURE COMMUNICATIONS
卷 10, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-019-13527-1
关键词
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资金
- I-CORE Gene Regulation in Complex Human Disease [41/11]
- Fritz Thyssen Stiftung
- Dalya Gridinger Fund
- Charles Clore Foundation
- European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program [726225]
- Israel Science Foundation [ISF 562/16, ISF 142/13, ISF Bikura 838/10]
- Cooperation Program in Cancer Research of the Deutsches Krebsforschungszentrum (DKFZ)
- Israel's Ministry of Science and Technology (MOST) [3-13112]
- Marie Curie Career Integration Grants (CIG)
- European Research Council (ERC) [726225] Funding Source: European Research Council (ERC)
MicroRNA (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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