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Nonsense-mediated mRNA decay safeguards telomeres in pluripotent stem cells - PubMed

4 hours ago
  • #NMD
  • #telomeres
  • #pluripotent stem cells
  • Telomeres are protective DNA caps at chromosome ends that prevent cells from mistakenly recognizing them as broken DNA.
  • Shelterin, a protein complex, safeguards telomeres, with TRF2 (encoded by Trf2) being a key component.
  • In mouse embryonic stem cells, TRF2 is not essential for telomere protection, indicating other compensatory mechanisms.
  • Nonsense-mediated mRNA decay (NMD), a cellular quality control system, plays an unexpected role in maintaining telomere integrity in pluripotent cells.
  • A genome-wide genetic screen revealed that NMD is essential for cell survival in the absence of TRF2.
  • NMD degrades an aberrant form of Trf1 mRNA, preventing the production of a harmful, truncated version of TRF1 that disrupts telomere protection.
  • This study reveals a unique strategy in embryonic stem cells for chromosome end protection, linking RNA quality control to genome stability.