N-methyladenosine Regulates the Stability of RNA:DNA Hybrids in Human Cells

Overview

Journal Nat Genet

Specialty Genetics

Date 2019 Dec 18

PMID 31844323

Citations 105

Authors

Abdulkadir Abakir

Tom C Giles

Agnese Cristini

Jeremy M Foster

Nan Dai

Marta Starczak

Alejandro Rubio-Roldan

Miaomiao Li

Maria Eleftheriou

James Crutchley

Luke Flatt

Lorraine Young

Daniel J Gaffney

Chris Denning

Bjorn Dalhus

Richard D Emes

Daniel Gackowski

Ivan R Correa Jr

Jose L Garcia-Perez

Arne Klungland

Natalia Gromak

Alexey Ruzov

Affiliations

Soon will be listed here.

Abstract

R-loops are nucleic acid structures formed by an RNA:DNA hybrid and unpaired single-stranded DNA that represent a source of genomic instability in mammalian cells. Here we show that N-methyladenosine (mA) modification, contributing to different aspects of messenger RNA metabolism, is detectable on the majority of RNA:DNA hybrids in human pluripotent stem cells. We demonstrate that mA-containing R-loops accumulate during G/M and are depleted at G/G phases of the cell cycle, and that the mA reader promoting mRNA degradation, YTHDF2 (ref. ), interacts with R-loop-enriched loci in dividing cells. Consequently, YTHDF2 knockout leads to increased R-loop levels, cell growth retardation and accumulation of γH2AX, a marker for DNA double-strand breaks, in mammalian cells. Our results suggest that mA regulates accumulation of R-loops, implying a role for this modification in safeguarding genomic stability.

Citing Articles

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