TRM6/61 connects PKCα with translational control through tRNAiMet stabilization: impact on tumorigenesis

Francoise Macari; Y El-Houfi; G Boldina; Hao Xu; S Khoury-Hanna; J Ollier; L Yazdani; Gang Zheng; I Bièche; Noémie Legrand; Damien Paulet; S Durrieu; A Byström; Stéphane Delbecq; Bernard Lapeyre; L Bauchet; J Pannequin; F Hollande; T Pan; M Teichmann; S Vagner; A David; A Choquet; D Joubert

doi:10.1038/onc.2015.244

Journal articles

TRM6/61 connects PKCα with translational control through tRNAiMet stabilization: impact on tumorigenesis

Francoise Macari ^{1, 2} Y El-Houfi ^{2, 1} G Boldina ^{3, 4} Hao Xu ⁵ S Khoury-Hanna ^{2, 1} J Ollier ^{2, 1} L Yazdani ^{2, 1} Gang Zheng ⁶ I Bièche ⁷ Noémie Legrand ^{2, 1} Damien Paulet ⁸ S Durrieu ^{9, 10} A Byström ⁵ Stéphane Delbecq ¹¹ Bernard Lapeyre ^{12, 13} L Bauchet ¹⁴ J Pannequin ^{2, 1} F Hollande ^{2, 15} T Pan ⁶ M Teichmann ⁹ S Vagner ^{3, 4} A David ^{2, 1} A Choquet ^{2, 1} D Joubert ^{2, 1}

1 UM - Université de Montpellier

2 IGF - Institut de Génomique Fonctionnelle

3 Stress génotoxiques et cancer

4 PSL - PSL Research University

5 Department of Molecular Biology [Umeå]

6 Department of Biochemistry and Molecular Biology

7 CRLCC René Huguenin

8 MAB - Méthodes et Algorithmes pour la Bioinformatique

LIRMM - Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier

9 Institut Européen de Chimie et de Biologie

10 UMR TETIS - Territoires, Environnement, Télédétection et Information Spatiale

11 LBCM - Vaccination Antiparasitaire : Laboratoire de Biologie Cellulaire et Moléculaire

12 CRIOBE - Centre de recherches insulaires et observatoire de l'environnement

13 CRBM - Centre de recherche en Biologie Cellulaire

14 Neurochirurgie [Hôpital Gui de Chauliac]

15 Molecular Mechanisms of Tumor Progression Laboratory

Abstract : 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 (tRNAiMet), 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 tRNAiMet. In contrast, elevated TRM6/61 expression regulated the translation of a subset of mRNAs encoding proteins involved in the tumorigenic process and increased the ability of C6 cells to form colonies in soft agar or spheres when grown in suspension. In TRM6/61/tRNAiMet-overexpressing cells, PKCα overexpression decreased tRNAiMet expression and both colony- and sphere-forming potentials. A concomitant increase in TRM6/TRM61 mRNA and tRNAiMet expression with decreased expression of PKCα mRNA was detected in highly aggressive glioblastoma multiforme as compared with Grade II/III glioblastomas, highlighting the clinical relevance of our findings. Altogether, we suggest that PKCα tightly controls TRM6/61 activity to prevent translation deregulation that would favor neoplastic development.

Document type :

Journal articles

Domain :

Engineering Sciences [physics]

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https://hal-univ-perp.archives-ouvertes.fr/hal-01224206
Contributor : Olivier Savoyat <>
Submitted on : Wednesday, November 4, 2015 - 11:45:27 AM
Last modification on : Thursday, July 2, 2020 - 2:01:42 PM

TRM6/61 connects PKCα with translational control through tRNAiMet stabilization: impact on tumorigenesis

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TRM6/61 connects PKCα with translational control through tRNAiMet stabilization: impact on tumorigenesis

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