Background: N6-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.

ADAR1 is a new target of METTL3 and plays a pro-oncogenic role in glioblastoma by an editing-independent mechanism / Tassinari, Valentina; Cesarini, Valeriana; Tomaselli, Sara; Ianniello, Zaira; Silvestris, Domenico Alessandro; Ginistrelli, Lavinia Ceci; Martini, Maurizio; De Angelis, Biagio; De Luca, Gabriele; Vitiani, Lucia Ricci; Fatica, Alessandro; Locatelli, Franco; Gallo, Angela. - In: GENOME BIOLOGY. - ISSN 1474-760X. - 22:1(2021), pp. 1-22. [10.1186/s13059-021-02271-9]

ADAR1 is a new target of METTL3 and plays a pro-oncogenic role in glioblastoma by an editing-independent mechanism

Tassinari, Valentina;Ianniello, Zaira;Fatica, Alessandro;Locatelli, Franco;
2021

Abstract

Background: N6-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.
2021
ADAR1; METTL3; RNA editing; glioblastoma
01 Pubblicazione su rivista::01a Articolo in rivista
ADAR1 is a new target of METTL3 and plays a pro-oncogenic role in glioblastoma by an editing-independent mechanism / Tassinari, Valentina; Cesarini, Valeriana; Tomaselli, Sara; Ianniello, Zaira; Silvestris, Domenico Alessandro; Ginistrelli, Lavinia Ceci; Martini, Maurizio; De Angelis, Biagio; De Luca, Gabriele; Vitiani, Lucia Ricci; Fatica, Alessandro; Locatelli, Franco; Gallo, Angela. - In: GENOME BIOLOGY. - ISSN 1474-760X. - 22:1(2021), pp. 1-22. [10.1186/s13059-021-02271-9]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1486471
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