The RNA-binding proteins CELF1 and ELAVL1 cooperatively control the alternative splicing of CD44.
CD44
Cancer
Gene expression
Post-transcriptional control
RNA-binding protein
Journal
Biochemical and biophysical research communications
ISSN: 1090-2104
Titre abrégé: Biochem Biophys Res Commun
Pays: United States
ID NLM: 0372516
Informations de publication
Date de publication:
20 10 2022
20 10 2022
Historique:
received:
11
07
2022
revised:
18
07
2022
accepted:
19
07
2022
pubmed:
17
8
2022
medline:
9
9
2022
entrez:
16
8
2022
Statut:
ppublish
Résumé
CD44 mRNA contains nine consecutive cassette exons, v2 to v10. Upon alternative splicing, several isoforms are produced with different impacts on tumor biology. Here, we demonstrate the involvement of the RNA-binding proteins CELF1 and ELAVL1 in the control of CD44 splicing. We show by FRET-FLIM that these proteins directly interact in the nucleus. By combining RNAi-mediated depletion and exon array hybridization in HeLa cells, we observe that the exons v7 to v10 of CD44 are highly sensitive to CELF1 and ELAVL1 depletion. We confirm by RT-PCR that CELF1 and ELAVL1 together stimulate the inclusion of these exons in CD44 mRNA. Finally, we show in eight different tumor types that high expression of CELF1 and/or ELAVL1 is correlated with the inclusion of CD44 variable exons. These data point to functional interactions between CELF1 and ELAVL1 in the control of CD44 splicing in human cancers.
Identifiants
pubmed: 35973378
pii: S0006-291X(22)01050-6
doi: 10.1016/j.bbrc.2022.07.073
pii:
doi:
Substances chimiques
CD44 protein, human
0
CELF1 Protein
0
CELF1 protein, human
0
ELAV-Like Protein 1
0
ELAVL1 protein, human
0
Hyaluronan Receptors
0
RNA, Messenger
0
RNA-Binding Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
79-84Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.