A role for AKT1 in nonsense-mediated mRNA decay

Martine Palma (1, 2) , Catherine Leroy (1, 2) , Sophie Salomé-Desnoulez (3) , Elisabeth Werkmeister (3, 4) , Rebekah Kong (1, 2) , Marc Mongy (3) , Hervé Le hir (5) , Fabrice Lejeune (1, 2)

1 CANTHER - Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277
2 Institut Pasteur de Lille
3 PLBS - Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41
4 CIIL - Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204
5 IBENS - Institut de biologie de l'ENS Paris

Nonsense-mediated mRNA decay (NMD) is a highly regulated quality control mechanism through which mRNAs harboring a premature termination codon are degraded. It is also a regulatory pathway for some genes. This mechanism is subject to various levels of regulation, including phosphorylation. To date only one kinase, SMG1, has been described to participate in NMD, by targeting the central NMD factor UPF1. Here, screening of a kinase inhibitor library revealed as putative NMD inhibitors several molecules targeting the protein kinase AKT1. We present evidence demonstrating that AKT1, a central player in the PI3K/AKT/mTOR signaling pathway, plays an essential role in NMD, being recruited by the UPF3X protein to phosphorylate UPF1. As AKT1 is often overactivated in cancer cells and as this should result in increased NMD efficiency, the possibility that this increase might affect cancer processes and be targeted in cancer therapy is discussed.

Domaines: Sciences du Vivant [q-bio]

Martine Palma, Catherine Leroy, Sophie Salomé-Desnoulez, Elisabeth Werkmeister, Rebekah Kong, et al.. A role for AKT1 in nonsense-mediated mRNA decay. Nucleic Acids Research, 2021, 49 (19), pp.11022-11037. ⟨10.1093/nar/gkab882⟩. ⟨hal-03423347⟩