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Publication : DNA methylation directs microRNA biogenesis in mammalian cells.

First Author  Glaich O Year  2019
Journal  Nat Commun Volume  10
Issue  1 Pages  5657
PubMed ID  31827083 Mgi Jnum  J:283936
Mgi Id  MGI:6387957 Doi  10.1038/s41467-019-13527-1
Citation  Glaich O, et al. (2019) DNA methylation directs microRNA biogenesis in mammalian cells. Nat Commun 10(1):5657
abstractText  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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