Miniatura

Fitxers

SerratX.pdf (2.9 MB)

Tipus de document

Article

Versió

Versió publicada

Data de publicació

2019-10-01

Llicència de publicació

cc by (c) Serrat, Xènia et al., 2019
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/170449

CRISPR editing of sftb-1/SF3B1 in Caenorhabditis elegans allows the identification of synthetic interactions with cancer-related mutations and the chemical inhibition of splicing

Títol de la revista

Autors

Director/Tutor

ISSN de la revista

Títol del volum

Recurs relacionat

https://doi.org/10.1371/journal.pgen.1008464

Resum

SF3B1 is the most frequently mutated splicing factor in cancer. Mutations in SF3B1 likely confer clonal advantages to cancer cells but they may also confer vulnerabilities that can be therapeutically targeted. SF3B1 cancer mutations can be maintained in homozygosis in C. elegans, allowing synthetic lethal screens with a homogeneous population of animals. These mutations cause alternative splicing (AS) defects in C. elegans, as it occurs in SF3B1-mutated human cells. In a screen, we identified RNAi of U2 snRNP components that cause synthetic lethality with sftb-1/SF3B1 mutations. We also detected synthetic interactions between sftb-1 mutants and cancer-related mutations in uaf-2/U2AF1 or rsp-4/SRSF2, demonstrating that this model can identify interactions between mutations that are mutually exclusive in human tumors. Finally, we have edited an SFTB-1 domain to sensitize C. elegans to the splicing modulators pladienolide B or herboxidiene. Thus, we have established a multicellular model for SF3B1 mutations amenable for high-throughput genetic and chemical screens.

Descripció

Matèries

Mutació (Biologia), Càncer

Matèries (anglès)

Mutation (Biology), Cancer

Citació

Col·leccions

Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citació

SERRAT, Xènia, KUKHTAR, Dmytro, CORNES, Eric, ESTEVE CODINA, Anna, BENLLOCH, Helena, CECERE, Germano, CERÓN MADRIGAL, Julián. CRISPR editing of sftb-1/SF3B1 in Caenorhabditis elegans allows the identification of synthetic interactions with cancer-related mutations and the chemical inhibition of splicing. _Plos Genetics_. 2019-10-01. Vol. 15, núm. Issue 10. [consulta: 10 de desembre de 2025]. [Disponible a: https://hdl.handle.net/2445/170449]

Exportar metadades

JSON - METS

Compartir registre