DNA methylation directs microRNA biogenesis in mammalian cells

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 Ast; Carmit Levy

doi:10.1038/s41467-019-13527-1

DNA methylation directs microRNA biogenesis in mammalian cells

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 Ast^*, Carmit Levy

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

95 Scopus citations

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.

Original language	English
Article number	5657
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-13527-1
State	Published - 1 Dec 2019
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2019, The Author(s).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s41467-019-13527-1

Cite this

@article{0e73478c6c074e65b31fbaf029d8094e,

title = "DNA methylation directs microRNA biogenesis in mammalian cells",

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.",

author = "Ohad Glaich and Shivang Parikh and Bell, {Rachel E.} and Keren Mekahel and Maya Donyo and Yodfat Leader and Ronna Shayevitch and Danna Sheinboim and Sivan Yannai and Dror Hollander and Ze{\textquoteright}ev Melamed and Galit Lev-Maor and Gil Ast and Carmit Levy",

note = "Publisher Copyright: {\textcopyright} 2019, The Author(s).",

year = "2019",

month = dec,

day = "1",

doi = "10.1038/s41467-019-13527-1",

language = "אנגלית",

volume = "10",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

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

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

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 31827083

AN - SCOPUS:85076420452

SN - 2041-1723

VL - 10

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 5657

ER -

DNA methylation directs microRNA biogenesis in mammalian cells

Abstract

Bibliographical note

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this