Mechanism of activation of methyltransferases involved in translation by the Trm112 'hub' protein.

Dominique Liger (1, 2) , Liliana Mora (3) , Noureddine Lazar (1, 2) , Sabine Figaro (3) , Julien Henri (1) , Nathalie Scrima (3) , Richard H Buckingham (3) , Herman van Tilbeurgh (2, 1) , Valérie Heurgué-Hamard (3) , Marc Graille (1)

1 IBBMC - Institut de biochimie et biophysique moléculaire et cellulaire
2 FAAM - Fonction et Architecture des Assemblages Macromoléculaires
3 REGCM - Régulation de l'expression génétique chez les microorganismes - Expression génétique microbienne

Methylation is a common modification encountered in DNA, RNA and proteins. It plays a central role in gene expression, protein function and mRNA translation. Prokaryotic and eukaryotic class I translation termination factors are methylated on the glutamine of the essential and universally conserved GGQ motif, in line with an important cellular role. In eukaryotes, this modification is performed by the Mtq2-Trm112 holoenzyme. Trm112 activates not only the Mtq2 catalytic subunit but also two other tRNA methyltransferases (Trm9 and Trm11). To understand the molecular mechanisms underlying methyltransferase activation by Trm112, we have determined the 3D structure of the Mtq2-Trm112 complex and mapped its active site. Using site-directed mutagenesis and in vivo functional experiments, we show that this structure can also serve as a model for the Trm9-Trm112 complex, supporting our hypothesis that Trm112 uses a common strategy to activate these three methyltransferases.

Domaines: Sciences du Vivant [q-bio]

Dominique Liger, Liliana Mora, Noureddine Lazar, Sabine Figaro, Julien Henri, et al.. Mechanism of activation of methyltransferases involved in translation by the Trm112 'hub' protein.. Nucleic Acids Research, 2011, 39 (14), pp.6249-59. ⟨10.1093/nar/gkr176⟩. ⟨hal-01430309⟩