Systematic Analysis of Targets of Pumilio-Mediated mRNA Decay Reveals that PUM1 Repression by DNA Damage Activates Translesion Synthesis.
Cell Rep
; 31(5): 107542, 2020 05 05.
Article
em En
| MEDLINE
| ID: mdl-32375027
ABSTRACT
RNA-binding proteins (RBPs) play a pivotal role in gene expression by modulating the stability of transcripts. However, the identification of degradation target mRNAs of RBPs remains difficult. By the combined analysis of transcriptome-wide mRNA stabilities and the binding of mRNAs to human Pumilio 1 (PUM1), we identify 48 mRNAs that both bind to PUM1 and exhibit PUM1-dependent degradation. Analysis of changes in the abundance of PUM1 and its degradation target mRNAs in RNA-seq data indicate that DNA-damaging agents negatively regulate PUM1-mediated mRNA decay. Cells exposed to cisplatin have reduced PUM1 abundance and increased PCNA and UBE2A mRNAs encoding proteins involved in DNA damage tolerance by translesion synthesis (TLS). Cells overexpressing PUM1 exhibit impaired DNA synthesis and TLS and increased sensitivity to the cytotoxic effect of cisplatin. Thus, our method identifies target mRNAs of PUM1-mediated decay and reveals that cells respond to DNA damage by inhibiting PUM1-mediated mRNA decay to activate TLS.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Dano ao DNA
/
RNA Mensageiro
/
Proteínas de Ligação a RNA
/
Regulação da Expressão Gênica no Desenvolvimento
/
Estabilidade de RNA
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article