FTO m6A RNA demethylase is important for proper DNA replication in human cells, TALK, Heidelberg, The epitranscriptome

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F25%3A00143662" target="_blank" >RIV/00216224:14740/25:00143662 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.embl.org/about/info/course-and-conference-office/events/etc25-01/#vf-tabs__section-overview" target="_blank" >https://www.embl.org/about/info/course-and-conference-office/events/etc25-01/#vf-tabs__section-overview</a>

DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

FTO m6A RNA demethylase is important for proper DNA replication in human cells, TALK, Heidelberg, The epitranscriptome

Popis výsledku v původním jazyce

N6-methyladenosine (m6A) and N6-2’-O-dimethyladenosine (m6Am) are two highly prevalent and dynamic eukaryotic mRNA modifications that exert regulatory effects on multiple steps of mRNA metabolism. m6A, in particular, has also been shown to regulate a vast majority of different cellular processes, including their newly identified roles in the maintenance of genome stability. Here, we demonstrate that FTO, an RNA demethylase of m6A and m6Am, is a critical player in replication fork dynamics. Our omics studies reveal physical and genetic interactions between FTO and DNA replication factors. We identify that FTO is physically present at sites of active replication and its demethylation activity is critical for normal replication fork progression. Under conditions of replication stress, FTO exercises a protective role over stalled replication forks to prevent the degradation of nascent DNA. Prolonged replication stress in the absence of FTO was seen to result in DNA strand breaks, possibly due to the collapse of stalled replication forks. Collectively, our results demonstrate a previously unknown role of FTO in the maintenance of replication fork integrity and provide a potential link between RNA modifications and DNA replication.

Název v anglickém jazyce

FTO m6A RNA demethylase is important for proper DNA replication in human cells, TALK, Heidelberg, The epitranscriptome

Popis výsledku anglicky

N6-methyladenosine (m6A) and N6-2’-O-dimethyladenosine (m6Am) are two highly prevalent and dynamic eukaryotic mRNA modifications that exert regulatory effects on multiple steps of mRNA metabolism. m6A, in particular, has also been shown to regulate a vast majority of different cellular processes, including their newly identified roles in the maintenance of genome stability. Here, we demonstrate that FTO, an RNA demethylase of m6A and m6Am, is a critical player in replication fork dynamics. Our omics studies reveal physical and genetic interactions between FTO and DNA replication factors. We identify that FTO is physically present at sites of active replication and its demethylation activity is critical for normal replication fork progression. Under conditions of replication stress, FTO exercises a protective role over stalled replication forks to prevent the degradation of nascent DNA. Prolonged replication stress in the absence of FTO was seen to result in DNA strand breaks, possibly due to the collapse of stalled replication forks. Collectively, our results demonstrate a previously unknown role of FTO in the maintenance of replication fork integrity and provide a potential link between RNA modifications and DNA replication.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/EH22_008%2F0004575" target="_blank" >EH22_008/0004575: RNA pro terapii</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů