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

Author:

Wang Yajun12,Zhu Wei1,Jang Yumi3,Sommers Joshua A4,Yi Gong1,Puligilla Chandrakala1,Croteau Deborah L1,Yang Yibin2,Kai Mihoko3,Liu Yie1ORCID

Affiliation:

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

Abstract

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.

Funder

National Institute on Aging

Publisher

Oxford University Press (OUP)

Subject

Genetics

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