The splicing factor CCAR1 regulates the Fanconi anemia/BRCA pathway.
Mol Cell
; 84(14): 2618-2633.e10, 2024 Jul 25.
Article
de En
| MEDLINE
| ID: mdl-39025073
ABSTRACT
The twenty-three Fanconi anemia (FA) proteins cooperate in the FA/BRCA pathway to repair DNA interstrand cross-links (ICLs). The cell division cycle and apoptosis regulator 1 (CCAR1) protein is also a regulator of ICL repair, though its possible function in the FA/BRCA pathway remains unknown. Here, we demonstrate that CCAR1 plays a unique upstream role in the FA/BRCA pathway and is required for FANCA protein expression in human cells. Interestingly, CCAR1 co-immunoprecipitates with FANCA pre-mRNA and is required for FANCA mRNA processing. Loss of CCAR1 results in retention of a poison exon in the FANCA transcript, thereby leading to reduced FANCA protein expression. A unique domain of CCAR1, the EF hand domain, is required for interaction with the U2AF heterodimer of the spliceosome and for excision of the poison exon. Taken together, CCAR1 is a splicing modulator required for normal splicing of the FANCA mRNA and other mRNAs involved in various cellular pathways.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Épissage des ARN
/
Protéines du cycle cellulaire
/
Protéines régulatrices de l'apoptose
/
Protéine du groupe de complémentation A de l'anémie de Fanconi
/
Anémie de Fanconi
/
Facteur d'épissage U2AF
Limites:
Humans
Langue:
En
Journal:
Mol Cell
Sujet du journal:
BIOLOGIA MOLECULAR
Année:
2024
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique
Pays de publication:
États-Unis d'Amérique