The RNA-binding motif protein 14 regulates telomere integrity at the interface of TERRA and telomeric R-loops

  • Nucleic Acids Res. 2023 Nov 1:gkad967. doi: 10.1093/nar/gkad967.
Yajun Wang  1  2 ,  Wei Zhu  1 ,  Yumi Jang  3 ,  Joshua A Sommers  4 ,  Gong Yi  1 ,  Chandrakala Puligilla  1 ,  Deborah L Croteau  1 ,  Yibin Yang  2 ,  Mihoko Kai  3 ,  Yie Liu  1
Affiliations
  • 1. Laboratory of Genetics and Genomics, 251 Bayview Blvd, National Institute on Aging/National Institutes of Health, Baltimore, MD 21224, USA.
  • 2. Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
  • 3. Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • 4. Translational Gerontology Branch, 251 Bayview Blvd, National Institute on Aging/National Institutes of Health, Baltimore, MD 21224, USA.
PMID: 37930826 DOI: 10.1093/nar/gkad967
Abstract

Telomeric repeat-containing RNA (TERRA) and its formation of RNA:DNA hybrids (or TERRA R-loops), influence telomere maintenance, particularly in human Cancer cells that use homologous recombination-mediated alternative lengthening of telomeres. Here, we report that the RNA-binding motif protein 14 (RBM14) is associated with telomeres in human Cancer cells. RBM14 negatively regulates TERRA expression. It also binds to TERRA and inhibits it from forming TERRA R-loops at telomeres. RBM14 depletion has several effects, including elevated TERRA levels, telomeric R-loops, telomere dysfunction-induced DNA damage foci formation, particularly in the presence of DNA replication stress, pRPA32 accumulation at telomeres and telomere signal-free ends. Thus, RBM14 protects telomere integrity via modulating TERRA levels and its R-loop formation at telomeres.

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