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DNA methylation directs microRNA biogenesis in mammalian cells

Author

Listed:
  • Ohad Glaich

    (Sackler Faculty of Medicine)

  • Shivang Parikh

    (Sackler Faculty of Medicine)

  • Rachel E. Bell

    (Sackler Faculty of Medicine)

  • Keren Mekahel

    (Sackler Faculty of Medicine)

  • Maya Donyo

    (Sackler Faculty of Medicine)

  • Yodfat Leader

    (Sackler Faculty of Medicine)

  • Ronna Shayevitch

    (Sackler Faculty of Medicine)

  • Danna Sheinboim

    (Sackler Faculty of Medicine)

  • Sivan Yannai

    (Sackler Faculty of Medicine)

  • Dror Hollander

    (Sackler Faculty of Medicine)

  • Ze’ev Melamed

    (Sackler Faculty of Medicine
    University of California at San Diego)

  • Galit Lev-Maor

    (Sackler Faculty of Medicine)

  • Gil Ast

    (Sackler Faculty of Medicine)

  • Carmit Levy

    (Sackler Faculty of Medicine)

Abstract

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.

Suggested Citation

  • Ohad Glaich & Shivang Parikh & Rachel E. Bell & Keren Mekahel & Maya Donyo & Yodfat Leader & Ronna Shayevitch & Danna Sheinboim & Sivan Yannai & Dror Hollander & Ze’ev Melamed & Galit Lev-Maor & Gil A, 2019. "DNA methylation directs microRNA biogenesis in mammalian cells," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13527-1
    DOI: 10.1038/s41467-019-13527-1
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