TRM6/61 connects PKC alpha with translational control through tRNA(i)(Met) stabilization: impact on tumorigenesis
F Macari, Y El-houfi, G Boldina, H Xu, S Khoury-Hanna, J Ollier, L Yazdani, G Zheng, I Bieche, N Legrand, D Paulet, S Durrieu, A Bystrom, S Delbecq, B Lapeyre, L Bauchet, J Pannequin, F Hollande, T Pan, M Teichmann Show all
ONCOGENE | NATURE PUBLISHING GROUP | Published : 2016
Accumulating evidence suggests that changes of the protein synthesis machinery alter translation of specific mRNAs and participate in malignant transformation. Here we show that protein kinase C α (PKCα) interacts with TRM61, the catalytic subunit of the TRM6/61 tRNA methyltransferase. The TRM6/61 complex is known to methylate the adenosine 58 of the initiator methionine tRNA (tRNAi(Met)), a nuclear post-transcriptional modification associated with the stabilization of this crucial component of the translation-initiation process. Depletion of TRM6/61 reduced proliferation and increased death of C6 glioma cells, effects that can be partially rescued by overexpression of tRNAi(Met). In contras..View full abstract
Awarded by Swedish Cancer Foundation
Awarded by Swedish Research Council
Awarded by Karin and Harald Silvanders Foundation
This work was generously supported by the Institut National du Cancer (INCa) and the Fondation ARC. We thank Martial Seveno, Serge Urbach and Edith Demettre from the 'Plate-forme de Proteomique Fonctionnelle' (FPP) for their work on proteomic analysis of cell samples. We thank the Gustave Roussy Genomic Core Facility (Noemie Pata-Merci) and the Gustave Roussy Bioinformatic Core Facility (Guillaume Meurice). ASB is supported by grants from the Swedish Cancer Foundation (13 0301), Swedish Research Council (621-2012-3576) and Karin and Harald Silvanders Foundation (223-2808-12).