The RNA-binding motif protein 14 regulates telomere integrity at the interface of TERRA and telomeric R-loops.
Nucleic Acids Res
; 51(22): 12242-12260, 2023 Dec 11.
Article
em En
| MEDLINE
| ID: mdl-37930826
ABSTRACT
Telomeric repeat-containing RNA (TERRA) and its formation of RNADNA 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Telômero
/
Homeostase do Telômero
Limite:
Humans
Idioma:
En
Revista:
Nucleic Acids Res
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos