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

Yajun Wang; Wei Zhu; Yumi Jang; Joshua A. Sommers; Gong Yi; Chandrakala  Puligilla; Deborah L. Croteau; Y. Yang; Mihoko Kai; Yie Liu

doi:10.1093/nar/gkad967

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

Yajun Wang
, Wei Zhu
, Yumi Jang
, Joshua A. Sommers
, Gong Yi
, Chandrakala Puligilla
, Deborah L. Croteau
, Y. Yang
, Mihoko Kai
, Yie Liu

Fox Chase Cancer Center
National Institute on Aging, Baltimore, MD, United States
Johns Hopkins University School of Medicine
National Institute on Aging

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

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.

Original language	English
Pages (from-to)	12242-12260
Number of pages	19
Journal	Nucleic Acids Research
Volume	51
Issue number	22
DOIs	https://doi.org/10.1093/nar/gkad967
State	Published - Dec 11 2023

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

DNA/genetics
Humans
Neoplasms/genetics
R-Loop Structures
RNA, Long Noncoding/genetics
RNA-Binding Motifs
RNA/genetics
Telomere Homeostasis
Telomere/genetics

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10.1093/nar/gkad967

https://www.ncbi.nlm.nih.gov/pubmed/37930826

Cite this

@article{c81921a7f78e4385bea84888e7d0a081,

title = "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.",

keywords = "DNA/genetics, Humans, Neoplasms/genetics, R-Loop Structures, RNA, Long Noncoding/genetics, RNA-Binding Motifs, RNA/genetics, Telomere Homeostasis, Telomere/genetics",

author = "Yajun Wang and Wei Zhu and Yumi Jang and Sommers, \{Joshua A.\} and Gong Yi and Chandrakala Puligilla and Croteau, \{Deborah L.\} and Y. Yang and Mihoko Kai and Yie Liu",

note = "{\textcopyright} The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research 2023.",

year = "2023",

month = dec,

day = "11",

doi = "10.1093/nar/gkad967",

language = "English",

volume = "51",

pages = "12242--12260",

journal = "Nucleic Acids Research",

issn = "0305-1048",

publisher = "Oxford University Press",

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TY - JOUR

T1 - The RNA-binding motif protein 14 regulates telomere integrity at the interface of TERRA and telomeric R-loops

AU - Wang, Yajun

AU - Zhu, Wei

AU - Jang, Yumi

AU - Sommers, Joshua A.

AU - Yi, Gong

AU - Puligilla, Chandrakala

AU - Croteau, Deborah L.

AU - Yang, Y.

AU - Kai, Mihoko

AU - Liu, Yie

N1 - © The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research 2023.

PY - 2023/12/11

Y1 - 2023/12/11

N2 - 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.

AB - 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.

KW - DNA/genetics

KW - Humans

KW - Neoplasms/genetics

KW - R-Loop Structures

KW - RNA, Long Noncoding/genetics

KW - RNA-Binding Motifs

KW - RNA/genetics

KW - Telomere Homeostasis

KW - Telomere/genetics

UR - https://www.scopus.com/pages/publications/85180011984

U2 - 10.1093/nar/gkad967

DO - 10.1093/nar/gkad967

M3 - Article

C2 - 37930826

SN - 0305-1048

VL - 51

SP - 12242

EP - 12260

JO - Nucleic Acids Research

JF - Nucleic Acids Research

IS - 22

ER -

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

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

Abstract

UN SDGs

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Access to Document

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Cell Culture Facility

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