TY  - JOUR
AU  - Glaich, Ohad
AU  - Parikh, Shivang
AU  - Bell, Rachel E
AU  - Mekahel, Keren
AU  - Donyo, Maya
AU  - Leader, Yodfat
AU  - Shayevitch, Ronna
AU  - Sheinboim, Danna
AU  - Yannai, Sivan
AU  - Hollander, Dror
AU  - Melamed, Ze'ev
AU  - Lev-Maor, Galit
AU  - Ast, Gil
AU  - Levy, Carmit
TI  - DNA methylation directs microRNA biogenesis in mammalian cells.
JO  - Nature Communications
VL  - 10
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Springer Nature
M1  - DKFZ-2025-02393
SP  - 5657
PY  - 2019
N1  - #DKFZ-MOST-Ca175#
AB  - 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.
KW  - Animals
KW  - Cell Line
KW  - DNA Methylation
KW  - Humans
KW  - Methyl-CpG-Binding Protein 2: genetics
KW  - Methyl-CpG-Binding Protein 2: metabolism
KW  - Mice
KW  - MicroRNAs: genetics
KW  - MicroRNAs: metabolism
KW  - Open Reading Frames
KW  - RNA Processing, Post-Transcriptional
KW  - Methyl-CpG-Binding Protein 2 (NLM Chemicals)
KW  - MicroRNAs (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:31827083
C2  - pmc:PMC6906426
DO  - DOI:10.1038/s41467-019-13527-1
UR  - https://inrepo02.dkfz.de/record/305776
ER  -