Functional significance of U2AF1 S34F mutations in lung adenocarcinomas.
Nat Commun
; 10(1): 5712, 2019 12 13.
Article
em En
| MEDLINE
| ID: mdl-31836708
ABSTRACT
The functional role of U2AF1 mutations in lung adenocarcinomas (LUADs) remains incompletely understood. Here, we report a significant co-occurrence of U2AF1 S34F mutations with ROS1 translocations in LUADs. To characterize this interaction, we profiled effects of S34F on the transcriptome-wide distribution of RNA binding and alternative splicing in cells harboring the ROS1 translocation. Compared to its wild-type counterpart, U2AF1 S34F preferentially binds and modulates splicing of introns containing CAG trinucleotides at their 3' splice junctions. The presence of S34F caused a shift in cross-linking at 3' splice sites, which was significantly associated with alternative splicing of skipped exons. U2AF1 S34F induced expression of genes involved in the epithelial-mesenchymal transition (EMT) and increased tumor cell invasion. Finally, S34F increased splicing of the long over the short SLC34A2-ROS1 isoform, which was also associated with enhanced invasiveness. Taken together, our results suggest a mechanistic interaction between mutant U2AF1 and ROS1 in LUAD.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Fusão Oncogênica
/
Processamento Alternativo
/
Fator de Processamento U2AF
/
Adenocarcinoma de Pulmão
/
Neoplasias Pulmonares
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article