Structural and functional insights into $Archaeoglobus\ fulgidus$ m$^2$G$_{10}$ tRNA methyltransferase Trm11 and its Trm112 activator - École polytechnique Access content directly
Journal Articles Nucleic Acids Research Year : 2020

Structural and functional insights into $Archaeoglobus\ fulgidus$ m$^2$G$_{10}$ tRNA methyltransferase Trm11 and its Trm112 activator

Abstract

tRNAs play a central role during the translation process and are heavily post-transcriptionally modified to ensure optimal and faithful mRNA decoding. These epitranscriptomics marks are added by largely conserved proteins and defects in the function of some of these enzymes are responsible for neurodevelopmental disorders and cancers. Here, we focus on the Trm11 enzyme, which forms N$^2$-methylguanosine (m$^2$G) at position 10 of several tRNAs in both archaea and eukaryotes. While eukaryotic Trm11 enzyme is only active as a complex with Trm112, an allosteric activator of methyltransferases modifying factors (RNAs and proteins) involved in mRNA translation, former studies have shown that some archaeal Trm11 proteins are active on their own. As these studies were performed on Trm11 enzymes originating from archaeal organisms lacking TRM112 gene, we have characterized Trm11 (AfTrm11) from the $Archaeoglobus\ fulgidus$ archaeon, which genome encodes for a Trm112 protein (AfTrm112). We show that AfTrm11 interacts directly with AfTrm112 similarly to eukaryotic enzymes and that although AfTrm11 is active as a single protein, its enzymatic activity is strongly enhanced by AfTrm112. We finally describe the first crystal structures of the AfTrm11-Trm112 complex and of Trm11, alone or bound to the methyltransferase inhibitor sinefungin.
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hal-03402458 , version 1 (25-10-2021)

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Can Wang, Nhan Van tran, Vincent Jactel, Vincent Guérineau, Marc Graille. Structural and functional insights into $Archaeoglobus\ fulgidus$ m$^2$G$_{10}$ tRNA methyltransferase Trm11 and its Trm112 activator. Nucleic Acids Research, 2020, 48 (19), pp.11068 - 11082. ⟨10.1093/nar/gkaa830⟩. ⟨hal-03402458⟩
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