ADAR1 is a new target of METTL3 and plays a pro-oncogenic role in glioblastoma by an editing-independent mechanism.
Journal
Genome biology
ISSN: 1474-760X
Titre abrégé: Genome Biol
Pays: England
ID NLM: 100960660
Informations de publication
Date de publication:
28 01 2021
28 01 2021
Historique:
received:
27
05
2020
accepted:
14
01
2021
entrez:
29
1
2021
pubmed:
30
1
2021
medline:
15
12
2021
Statut:
epublish
Résumé
N Here, we show that METTL3, upregulated in glioblastoma, methylates ADAR1 mRNA and increases its protein level leading to a pro-tumorigenic mechanism connecting METTL3, YTHDF1, and ADAR1. We show that ADAR1 plays a cancer-promoting role independently of its deaminase activity by binding CDK2 mRNA, underlining the importance of ADARs as essential RNA-binding proteins for cell homeostasis as well as cancer progression. Additionally, we show that ADAR1 knockdown is sufficient to strongly inhibit glioblastoma growth in vivo. Hence, our findings underscore METTL3/ADAR1 axis as a novel crucial pathway in cancer progression that connects m6A and A-to-I editing post-transcriptional events.
Sections du résumé
BACKGROUND
N
RESULTS
Here, we show that METTL3, upregulated in glioblastoma, methylates ADAR1 mRNA and increases its protein level leading to a pro-tumorigenic mechanism connecting METTL3, YTHDF1, and ADAR1. We show that ADAR1 plays a cancer-promoting role independently of its deaminase activity by binding CDK2 mRNA, underlining the importance of ADARs as essential RNA-binding proteins for cell homeostasis as well as cancer progression. Additionally, we show that ADAR1 knockdown is sufficient to strongly inhibit glioblastoma growth in vivo.
CONCLUSIONS
Hence, our findings underscore METTL3/ADAR1 axis as a novel crucial pathway in cancer progression that connects m6A and A-to-I editing post-transcriptional events.
Identifiants
pubmed: 33509238
doi: 10.1186/s13059-021-02271-9
pii: 10.1186/s13059-021-02271-9
pmc: PMC7842030
doi:
Substances chimiques
Protein Isoforms
0
RNA, Messenger
0
RNA-Binding Proteins
0
YTHDF1 protein, human
0
Methyltransferases
EC 2.1.1.-
METTL3 protein, human
EC 2.1.1.62
ADAR protein, human
EC 3.5.4.37
Adenosine Deaminase
EC 3.5.4.4
Adenosine
K72T3FS567
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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