RT Journal Article
T1 N6-methyladenosine regulates the stability of RNA:DNA hybrids in human cells.
A1 Abakir, Abdulkadir
A1 Giles, Tom C
A1 Cristini, Agnese
A1 Foster, Jeremy M
A1 Dai, Nan
A1 Starczak, Marta
A1 Rubio-Roldan, Alejandro
A1 Li, Miaomiao
A1 Eleftheriou, Maria
A1 Crutchley, James
A1 Flatt, Luke
A1 Young, Lorraine
A1 Gaffney, Daniel J
A1 Denning, Chris
A1 Dalhus, Bjørn
A1 Emes, Richard D
A1 Gackowski, Daniel
A1 Corrêa, Ivan R
A1 Garcia-Perez, Jose L
A1 Klungland, Arne
A1 Gromak, Natalia
A1 Ruzov, Alexey
AB 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 cells1-4. Here we show that N6-methyladenosine (m6A) modification, contributing to different aspects of messenger RNA metabolism5,6, is detectable on the majority of RNA:DNA hybrids in human pluripotent stem cells. We demonstrate that m6A-containing R-loops accumulate during G2/M and are depleted at G0/G1 phases of the cell cycle, and that the m6A reader promoting mRNA degradation, YTHDF2 (ref. 7), 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 m6A regulates accumulation of R-loops, implying a role for this modification in safeguarding genomic stability.
YR 2019
FD 2019-12-16
LK http://hdl.handle.net/10668/14837
UL http://hdl.handle.net/10668/14837
LA en
DS RISalud
RD Apr 20, 2025