TY - JOUR
T1 - DNA methylation directs microRNA biogenesis in mammalian cells
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
N1 - Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=85076420452&partnerID=8YFLogxK
U2 - 10.1038/s41467-019-13527-1
DO - 10.1038/s41467-019-13527-1
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C2 - 31827083
AN - SCOPUS:85076420452
SN - 2041-1723
VL - 10
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 5657
ER -
