Double-Stranded RNA Structural Elements Holding the Key to Translational Regulation in Cancer: The Case of Editing in RNA-Binding Motif Protein 8A.
3' Untranslated Regions
/ genetics
Adenosine Deaminase
/ metabolism
Animals
Cell Line, Tumor
Epithelium
/ metabolism
Genes, Reporter
Humans
Mesothelioma
/ genetics
Mice
Models, Biological
Protein Binding
Protein Biosynthesis
RNA Editing
RNA, Double-Stranded
/ chemistry
RNA-Binding Motifs
RNA-Binding Proteins
/ metabolism
Musashi
RNA editing
RNA-binding motif protein 8a
RNA-binding proteins
adenosine deaminase acting on dsRNA
mesothelioma
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
15 12 2021
15 12 2021
Historique:
received:
16
11
2021
revised:
08
12
2021
accepted:
13
12
2021
entrez:
24
12
2021
pubmed:
25
12
2021
medline:
8
1
2022
Statut:
epublish
Résumé
Mesothelioma is an aggressive cancer associated with asbestos exposure. RNA-binding motif protein 8a (RBM8A) mRNA editing increases in mouse tissues upon asbestos exposure. The aim of this study was to further characterize the role of RBM8A in mesothelioma and the consequences of its mRNA editing. RBM8A protein expression was higher in mesothelioma compared to mesothelial cells. Silencing RBM8A changed splicing patterns in mesothelial and mesothelioma cells but drastically reduced viability only in mesothelioma cells. In the tissues of asbestos-exposed mice, editing of Rbm8a mRNA was associated with increased protein immunoreactivity, with no change in mRNA levels. Increased adenosine deaminase acting on dsRNA (ADAR)-dependent editing of Alu elements in the RBM8A 3'UTR was observed in mesothelioma cells compared to mesothelial cells. Editing stabilized protein expression. The unedited RBM8A 3'UTR had a stronger interaction with Musashi (MSI) compared to the edited form. The silencing of MSI2 in mesothelioma or overexpression of Adar2 in mesothelial cells resulted in increased RBM8A protein levels. Therefore, ADAR-dependent editing contributes to maintaining elevated RBM8A protein levels in mesothelioma by counteracting MSI2-driven downregulation. A wider implication of this mechanism for the translational control of protein expression is suggested by the editing of similarly structured Alu elements in several other transcripts.
Identifiants
pubmed: 34944051
pii: cells10123543
doi: 10.3390/cells10123543
pmc: PMC8699885
pii:
doi:
Substances chimiques
3' Untranslated Regions
0
MSI2 protein, human
0
RBM8A protein, human
0
RNA, Double-Stranded
0
RNA-Binding Proteins
0
ADAR protein, human
EC 3.5.4.37
Adenosine Deaminase
EC 3.5.4.4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Swiss National Science Foundation
ID : 320030_182690
Pays : Switzerland
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