A high-throughput screen identifies small molecule modulators of alternative splicing by targeting RNA G-quadruplexes.
Nucleic Acids Res
; 47(7): 3667-3679, 2019 04 23.
Article
em En
| MEDLINE
| ID: mdl-30698802
ABSTRACT
RNA secondary structures have been increasingly recognized to play an important regulatory role in post-transcriptional gene regulation. We recently showed that RNA G-quadruplexes, which serve as cis-elements to recruit splicing factors, play a critical role in regulating alternative splicing during the epithelial-mesenchymal transition. In this study, we performed a high-throughput screen using a dual-color splicing reporter to identify chemical compounds capable of regulating G-quadruplex-dependent alternative splicing. We identify emetine and its analog cephaeline as small molecules that disrupt RNA G-quadruplexes, resulting in inhibition of G-quadruplex-dependent alternative splicing. Transcriptome analysis reveals that emetine globally regulates alternative splicing, including splicing of variable exons that contain splice site-proximal G-quadruplexes. Our data suggest the use of emetine and cephaeline for investigating mechanisms of G-quadruplex-associated alternative splicing.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
RNA
/
Splicing de RNA
/
Processamento Alternativo
/
Quadruplex G
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Nucleic Acids Res
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos