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

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.

SUBMITTER: Wang Y

PROVIDER: S-EPMC10711441 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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

Wang Yajun Y Zhu Wei W Jang Yumi Y Sommers Joshua A JA Yi Gong G Puligilla Chandrakala C Croteau Deborah L DL Yang Yibin Y Kai Mihoko M Liu Yie Y

Nucleic acids research 20231201 22

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 ...[more]

PMID: 37930826

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