Methyltransferase complex subunit METTL3 maintains genome stability of erythroid cells via MTHFD1-mediated nucleotide biosynthesis - PubMed
2 days ago
- #Erythropoiesis
- #Genome Stability
- #Nucleotide Biosynthesis
- Methyltransferase complex subunit METTL3 is crucial for maintaining genome stability in erythroid cells through MTHFD1-mediated nucleotide biosynthesis.
- Deletion of Mettl3 in mice leads to microcytic/hypochromic anemia, defective erythropoiesis, and impaired hemoglobin biosynthesis due to disrupted nucleotide biosynthesis and DNA damage.
- Mthfd1, a key enzyme in nucleotide biosynthesis, was identified as a direct target gene of Mettl3, with its deletion causing a shortage of nucleotides dTMP and IMP in erythroid cells.
- Inhibition of METTL3 in human erythroid cells results in similar phenotypic and molecular changes, indicating a conserved role across species.
- The study reveals a METTL3-m6A-MTHFD1 axis essential for erythropoiesis, offering insights into regulatory mechanisms and potential implications for understanding anemias.