Nature communications, 2019-12, Vol.10 (1), p.5657-11, Article 5657
2019
Details
- Autor(en) / Beteiligte
- Titel
- DNA methylation directs microRNA biogenesis in mammalian cells
- Ist Teil von
- Nature communications, 2019-12, Vol.10 (1), p.5657-11, Article 5657
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2019
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-019-13527-1Titel-ID: cdi_doaj_primary_oai_doaj_org_article_ace0740f21624dc8b8606e6fd012d471
- Format
- –
- Schlagworte
- Animals, Biosynthesis, Cell Line, Deoxyribonucleic acid, DNA, DNA Methylation, DNA-directed RNA polymerase, Elongation, Humans, Mammalian cells, Mammals, Methyl-CpG-Binding Protein 2 - genetics, Methyl-CpG-Binding Protein 2 - metabolism, Mice, MicroRNAs, MicroRNAs - genetics, MicroRNAs - metabolism, miRNA, Open Reading Frames, Ribonucleic acid, RNA, RNA polymerase, RNA polymerase II, RNA Processing, Post-Transcriptional, Transcription