N6-methyladenosine regulates the stability of RNA:DNA hybrids in human cells.
Nat Genet
; 52(1): 48-55, 2020 01.
Article
em 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
DNA
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RNA
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Adenosina
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Proteínas de Ligação a RNA
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Estabilidade de RNA
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Células-Tronco Pluripotentes
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Instabilidade Genômica
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article