title: Saccharomyces cerevisiae Eukaryotic Elongation Factor 1A (eEF1A) Is Methylated at Lys-390 by a METTL21-Like Methyltransferase.
abstract: The human methyltransferases (MTases) METTL21A and VCP-KMT (METTL21D) were recently shown to methylate single lysine residues in Hsp70 proteins and in VCP, respectively. The yet uncharacterized MTase encoded by the YNL024C gene in Saccharomyces cerevisiae shows high sequence similarity to METTL21A and VCP-KMT, as well as to their uncharacterized paralogues METTL21B and METTL21C. Despite being most similar to METTL21A, the Ynl024c protein does not methylate yeast Hsp70 proteins, which were found to be unmethylated on the relevant lysine residue. Eukaryotic translation elongation factor eEF1A in yeast has been reported to contain four methylated lysine residues (Lys30, Lys79, Lys318 and Lys390), and we here show that the YNL024C gene is required for methylation of eEF1A at Lys390, the only of these methylations for which the responsible MTase has not yet been identified. Lys390 was found in a partially monomethylated state in wild-type yeast cells but was exclusively unmethylated in a ynl024cΔ strain, and over-expression of Ynl024c caused a dramatic increase in Lys390 methylation, with trimethylation becoming the predominant state. Our results demonstrate that Ynl024c is the enzyme responsible for methylation of eEF1A at Lys390, and in accordance with prior naming of similar enzymes, we suggest that Ynl024c is renamed to Efm6 (Elongation factor MTase 6).
authors.affiliation: Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, 0316, Norway.
authors.forename: Magnus E
authors.initials: ME
authors.lastname: Jakobsson
authors.affiliation: Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, 0316, Norway.
authors.forename: Erna
authors.initials: E
authors.lastname: Davydova
authors.affiliation: Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, 0316, Norway.
authors.forename: Jędrzej
authors.initials: J
authors.lastname: Małecki
authors.affiliation: Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, 0316, Norway.
authors.forename: Anders
authors.initials: A
authors.lastname: Moen
authors.affiliation: Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, 0316, Norway.
authors.forename: Pål Ø
authors.initials: PØ
authors.lastname: Falnes
mesh_terms: D000595:Amino Acid Sequence; D015254:DNA Modification Methylases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D008780:Methyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D030781:Organisms, Genetically Modified; D020648:Peptide Elongation Factor 1 / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D020648:Peptide Elongation Factor 1; D029701:Saccharomyces cerevisiae Proteins; D015254:DNA Modification Methylases; C000622448:EEF1AKMT3 protein, human; C000607381:Efm6 protein, S cerevisiae; C585168:METTL21A protein, human; D008780:Methyltransferases; C577899:VCPKMT protein, human; D008239:Lysine