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N6-methyladenosine regulates the stability of RNA:DNA hybrids in human cells.
Abakir, Abdulkadir; Giles, Tom C; Cristini, Agnese; Foster, Jeremy M; Dai, Nan; Starczak, Marta; Rubio-Roldan, Alejandro; Li, Miaomiao; Eleftheriou, Maria; Crutchley, James; Flatt, Luke; Young, Lorraine; Gaffney, Daniel J; Denning, Chris; Dalhus, Bjørn; Emes, Richard D; Gackowski, Daniel; Corrêa, Ivan R; Garcia-Perez, Jose L; Klungland, Arne; Gromak, Natalia; Ruzov, Alexey.
Affiliation
  • Abakir A; Department of Stem Cell Biology, University of Nottingham, Nottingham, UK.
  • Giles TC; Advanced Data Analysis Centre, University of Nottingham, Sutton Bonington, UK.
  • Cristini A; Digital Research Service, University of Nottingham, Sutton Bonington, UK.
  • Foster JM; Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
  • Dai N; New England Biolabs, Inc., Ipswich, MA, USA.
  • Starczak M; New England Biolabs, Inc., Ipswich, MA, USA.
  • Rubio-Roldan A; Department of Clinical Biochemistry, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland.
  • Li M; GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, Granada, Spain.
  • Eleftheriou M; Department of Microbiology, Oslo University Hospital, Oslo, Norway.
  • Crutchley J; Department of Molecular Medicine, University of Oslo, Oslo, Norway.
  • Flatt L; Department of Stem Cell Biology, University of Nottingham, Nottingham, UK.
  • Young L; Department of Stem Cell Biology, University of Nottingham, Nottingham, UK.
  • Gaffney DJ; Department of Stem Cell Biology, University of Nottingham, Nottingham, UK.
  • Denning C; Department of Stem Cell Biology, University of Nottingham, Nottingham, UK.
  • Dalhus B; Wellcome Sanger Institute, Cambridge, UK.
  • Emes RD; Department of Stem Cell Biology, University of Nottingham, Nottingham, UK.
  • Gackowski D; Department of Microbiology, Oslo University Hospital, Oslo, Norway.
  • Corrêa IR; Department of Medical Biochemistry, University of Oslo, Oslo, Norway.
  • Garcia-Perez JL; Advanced Data Analysis Centre, University of Nottingham, Sutton Bonington, UK.
  • Klungland A; School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, UK.
  • Gromak N; Department of Clinical Biochemistry, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland.
  • Ruzov A; New England Biolabs, Inc., Ipswich, MA, USA.
Nat Genet ; 52(1): 48-55, 2020 01.
Article in En | MEDLINE | ID: mdl-31844323
ABSTRACT
R-loops are nucleic acid structures formed by an RNADNA 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 RNADNA 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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: DNA / RNA / Adenosine / RNA-Binding Proteins / RNA Stability / Pluripotent Stem Cells / Genomic Instability Limits: Animals / Humans Language: En Journal: Nat Genet Journal subject: GENETICA MEDICA Year: 2020 Document type: Article Affiliation country: United kingdom
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: DNA / RNA / Adenosine / RNA-Binding Proteins / RNA Stability / Pluripotent Stem Cells / Genomic Instability Limits: Animals / Humans Language: En Journal: Nat Genet Journal subject: GENETICA MEDICA Year: 2020 Document type: Article Affiliation country: United kingdom