| Autor: |
Valentina Tassinari, Valeriana Cesarini, Sara Tomaselli, Zaira Ianniello, Domenico Alessandro Silvestris, Lavinia Ceci Ginistrelli, Maurizio Martini, Biagio De Angelis, Gabriele De Luca, Lucia Ricci Vitiani, Alessandro Fatica, Franco Locatelli, Angela Gallo |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
Genome Biology, Vol 22, Iss 1, Pp 1-22 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
1474-760X |
| DOI: |
10.1186/s13059-021-02271-9 |
| Popis: |
Abstract Background N 6 -methyladenosine (m6A) and adenosine-to-inosine (A-to-I) RNA editing are two of the most abundant RNA modification events affecting adenosines in mammals. Both these RNA modifications determine mRNA fate and play a pivotal role in tumor development and progression. 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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