ARID1A loss promotes RNA editing of CDK13 in an ADAR1-dependent manner.
BMC Biol
; 22(1): 132, 2024 Jun 05.
Article
em En
| MEDLINE
| ID: mdl-38835016
ABSTRACT
BACKGROUND:
ARID1A, a subunit of the SWI/SNF chromatin remodeling complex, is thought to play a significant role both in tumor suppression and tumor initiation, which is highly dependent upon context. Previous studies have suggested that ARID1A deficiency may contribute to cancer development. The specific mechanisms of whether ARID1A loss affects tumorigenesis by RNA editing remain unclear.RESULTS:
Our findings indicate that the deficiency of ARID1A leads to an increase in RNA editing levels and alterations in RNA editing categories mediated by adenosine deaminases acting on RNA 1 (ADAR1). ADAR1 edits the CDK13 gene at two previously unidentified sites, namely Q113R and K117R. Given the crucial role of CDK13 as a cyclin-dependent kinase, we further observed that ADAR1 deficiency results in changes in the cell cycle. Importantly, the sensitivity of ARID1A-deficient tumor cells to SR-4835, a CDK12/CDK13 inhibitor, suggests a promising therapeutic approach for individuals with ARID1A-mutant tumors. Knockdown of ADAR1 restored the sensitivity of ARID1A deficient cells to SR-4835 treatment.CONCLUSIONS:
ARID1A deficiency promotes RNA editing of CDK13 by regulating ADAR1.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Adenosina Desaminase
/
Proteínas de Ligação a RNA
/
Edição de RNA
/
Quinases Ciclina-Dependentes
/
Proteínas de Ligação a DNA
Limite:
Humans
Idioma:
En
Revista:
BMC Biol
Assunto da revista:
BIOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article