Study of camptothecin- and cisplatin-induced alternative splicing events

Various genotoxic drugs used in cancer therapy induce alternative splicing or pre-messenger RNA. The nature and the intensity of alternative splicing was compared for Camptothecin, Cisplatin and

Role of the splicing factor SRSF4 in cisplatin-induced modifications of pre-mRNA splicing and apoptosis.

BACKGROUND: Modification of splicing by chemotherapeutic drugs has usually been evaluated on a limited number of pre-mRNAs selected for their recognized or potential importance in cell proliferation or apoptosis. However, the pathways linking splicing alterations to the efficiency of cancer therapy remain unclear. METHODS: Next-generation sequencing was used to analyse the transcriptome of breast carcinoma cells treated by cisplatin. Pharmacological inhibitors, RNA interference, cells deficient in specific signalling pathways, RT-PCR and FACS analysis were used to investigate how the anti-cancer drug cisplatin affected alternative splicing and the cell death pathway. RESULTS: We identified 717 splicing events affected by cisplatin, including 245 events involving cassette exons. Gene ontology analysis indicates that cell cycle, mRNA processing and pre-mRNA splicing were the main pathways affected. Importantly, the cisplatin–induced splicing alterations required class I PI3Ks P110β but not components such as ATM, ATR and p53 that are involved in the DNA damage response. The siRNA-mediated depletion of the splicing regulator SRSF4, but not SRSF6, expression abrogated many of the splicing alterations as well as cell death induced by cisplatin. CONCLUSION: Many of the splicing alterations induced by cisplatin are caused by SRSF4 and they contribute to apoptosis in a process requires class I PI3K. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1259-0) contains supplementary material, which is available to authorized users

Alternative splicing induced by cisplatin : Effect on mitochondria shape

Regulation of alternative splicing by chemotherapeutic agent

Study of molecular mechanisms of DNA Damage induced alternative splicing: implications in cancer therapy

ARC - Actions de recherche concertées; DNA damage-induced alternative splicing of gene transcripts: implications in cancer therapy, SPLICEOMI

A c-jun/splicing factors complex triggers altered pre-mRNA splcing in response to cisplatin

DNA lesions induce alternative splicing of hundreds of pre-messengers RNA. We established than c-Jun is required for this large scale reorganisation of the proteome after cisplatin treatment. .Alternative splicing induced by genotoxic antitumor agent

C-Jun régule l'épissage alternatif des ARn pré-messagers induit par le cisplatine

Genotoxic stress is a well-known inducer of pre-mRNa alternative splicing . In this work, we aim at identifying keys componants of the signaling cascade linking the DNA lesion to the splcing machiney.and thus gain better knowledge od the molecular mechanism controling large scale splcing decision in stress situation. Nous avons établi que C-Jun est important pour l'épissage alternatif de nombreux ARN pré-messagers.Epissage alternatif induit par les agents génotoxiques chimiothérapeutique

c-Jun : a new regulatory element for cisplatin induced alternative splicing

DNA damaging agents induce a large scale reorganisation of the proteome through pre messenger alternative splicing. We present evidence that c-Jun is required to induce this altered stress related proteome.Etude de l'épissage alternatif induit par les agents chimiotherpeutiques génotoxique