Adenosine (de)methylation on the crossroads of RNA and DNA synthesis

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F25%3A00143654" target="_blank" >RIV/00216224:14740/25:00143654 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.oeaw.ac.at/imba/seminars-events/microsymposium" target="_blank" >https://www.oeaw.ac.at/imba/seminars-events/microsymposium</a>

DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Adenosine (de)methylation on the crossroads of RNA and DNA synthesis

Popis výsledku v původním jazyce

Eukaryotic mRNAs are subject to significant chemical modifications that exhibit a multi-layered regulation of transcript metabolism. Among these, N6-methyladenosine (m6A) and N6-2’O-dimethyladenosine (m6Am) are two prevalent modifications in higher eukaryotes. The dynamics of these modifications are tightly governed by dedicated machineries, the perturbation of which destabilise cellular homeostasis. In a recent study using proximity-based labelling approach, we identified that m6A/m eraser protein – FTO – was proximally interacting with proteins in DNA replication and repair pathways. To elucidate this further, in this study we performed subsequent protein interaction assays and genome wide CRISPR screening, where we identified multiple candidates involved at different levels of DNA synthesis. Additionally, we performed functional assays to further investigate the relevance of FTO in these processes. Preliminary results from these functional assays positively correlate with our observations from the high throughput screening approaches, highlighting the importance of the m6A/m modifying enzyme, FTO, in the maintenance of genome integrity.

Název v anglickém jazyce

Adenosine (de)methylation on the crossroads of RNA and DNA synthesis

Popis výsledku anglicky

Eukaryotic mRNAs are subject to significant chemical modifications that exhibit a multi-layered regulation of transcript metabolism. Among these, N6-methyladenosine (m6A) and N6-2’O-dimethyladenosine (m6Am) are two prevalent modifications in higher eukaryotes. The dynamics of these modifications are tightly governed by dedicated machineries, the perturbation of which destabilise cellular homeostasis. In a recent study using proximity-based labelling approach, we identified that m6A/m eraser protein – FTO – was proximally interacting with proteins in DNA replication and repair pathways. To elucidate this further, in this study we performed subsequent protein interaction assays and genome wide CRISPR screening, where we identified multiple candidates involved at different levels of DNA synthesis. Additionally, we performed functional assays to further investigate the relevance of FTO in these processes. Preliminary results from these functional assays positively correlate with our observations from the high throughput screening approaches, highlighting the importance of the m6A/m modifying enzyme, FTO, in the maintenance of genome integrity.

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