The dual methyltransferase METTL13 targets N terminus and Lys55 of eEF1A and modulates codon-specific translation rates

  title={The dual methyltransferase METTL13 targets N terminus and Lys55 of eEF1A and modulates codon-specific translation rates},
  author={Magnus E. Jakobsson and Jędrzej M. Małecki and Levon Halabelian and Benedikt S Nilges and Rita Pinto and Srikanth Kudithipudi and Stephanie Munk and Erna Davydova and Fawzi Rahmadiyan Zuhairi and Cheryl H. Arrowsmith and Albert Jeltsch and Sebastian A. Leidel and Jesper Velgaard Olsen and P{\aa}l {\O}. Falnes},
  journal={Nature Communications},
Eukaryotic elongation factor 1 alpha (eEF1A) delivers aminoacyl-tRNA to the ribosome and thereby plays a key role in protein synthesis. Human eEF1A is subject to extensive post-translational methylation, but several of the responsible enzymes remain unknown. Using a wide range of experimental approaches, we here show that human methyltransferase (MTase)-like protein 13 (METTL13) contains two distinct MTase domains targeting the N terminus and Lys55 of eEF1A, respectively. Our biochemical and… 
Human METTL18 is a histidine-specific methyltransferase that targets RPL3 and affects ribosome biogenesis and function
METTL18 is established as the second human histidine-specific protein MTase, and its functional relevance is demonstrated, indicating that METTL18-mediated methylation of RPL3 is important for optimal ribosome biogenesis and function.
Structure, Activity and Function of the Dual Protein Lysine and Protein N-Terminal Methyltransferase METTL13
The current literature related to the structure, activity, and function of METTL13 is systematically reviewed and put into context and the links betweenMETTL13 and diseases, mainly different types of cancer, are summarized.
The human methyltransferase ZCCHC4 catalyses N6-methyladenosine modification of 28S ribosomal RNA
It is established that ZCCHC4 is the enzyme responsible for m6A modification of human 28S rRNA, and its functional significance in mRNA translation is demonstrated.
Methyltransferase-like 21C (METTL21C) methylates alanine tRNA synthetase at Lys-943 in muscle tissue
It is found that METTL21C catalyzes methylation of Lys-943 of AARS1 (AARS1-K943me) both in vitro and in vivo, and this results reveal that Aars1 is a bona fide in vitro substrate of MET TL21C and suggest a role for the METTL 21C-Aars1 axis in the regulation of protein synthesis in muscle tissue.
Human FAM173A is a mitochondrial lysine-specific methyltransferase that targets adenine nucleotide translocase and affects mitochondrial respiration
It is demonstrated that FAM173A is the long-sought KMT responsible for ANT methylation at Lys-52, and point out the functional significance of Lys- 52 methylation in ANT.
Evolution of Methyltransferase-Like (METTL) Proteins in Metazoa: A Complex Gene Family Involved in Epitranscriptomic Regulation and Other Epigenetic Processes
Evidence is provided that the long-term evolution of METTL family members was driven by strong purifying selection, which in combination with adaptive selection episodes, led to the functional specialization of individual METTL lineages.
Mettl17, a regulator of mitochondrial ribosomal RNA modifications, is required for the translation of mitochondrial coding genes
  • Zhennan Shi, Siyuan Xu, F. Lan
  • Biology
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2019
It is reported that methyltransferase like (Mettl) 17, identified from the clustered regularly interspaced short palindromic repeats knockout screen, is required for proper differentiation of mouse embryonic stem cells (mESCs).
Protein methylation in mitochondria
Eukaryote-Conserved Methylarginine Is Absent in Diplomonads and Functionally Compensated in Giardia
The results challenge the view that arginine methylation is eukaryote conserved and demonstrate that functional compensation of methylarginine was possible preceding expansion and diversification of these key networks in higher eUKaryotes.
mTORC1-independent translation control in mammalian cells by methionine adenosyltransferase 2A and S-adenosylmethionine


The novel lysine specific methyltransferase METTL21B affects mRNA translation through inducible and dynamic methylation of Lys-165 in human eukaryotic elongation factor 1 alpha (eEF1A)
It is demonstrated, using a wide range of in vitro and in vivo approaches, that the previously uncharacterized human methyltransferase METTL21B specifically targets Lys-165 in eEF1A in an aminoacyl-tRNA- and GTP-dependent manner and shows that this modification is dynamic, inducible and likely of regulatory importance.
Identification and Characterization of a Novel Evolutionarily Conserved Lysine-specific Methyltransferase Targeting Eukaryotic Translation Elongation Factor 2 (eEF2)*
The present study establishes the function of the previously uncharacterized MTases FAM86A and Yjr129c, demonstrating that these enzymes introduce a functionally important lysine methylation in eEF2.
Novel N-terminal and Lysine Methyltransferases That Target Translation Elongation Factor 1A in Yeast and Human*
A new eukaryotic protein N-terminal methyltransferase is reported, Saccharomyces cerevisiae YLR285W, which methylates eEF1A at a previously undescribed high-stoichiometry N-Terminal site and the adjacent lysine and is named Efm7.
Methylation of human eukaryotic elongation factor alpha (eEF1A) by a member of a novel protein lysine methyltransferase family modulates mRNA translation
It is demonstrated that an uncharacterized human 7BS MTase currently annotated as part of the endothelin converting enzyme 2, but which should be considered a separate enzyme efficiently methylates K36 in eukaryotic translation elongation factor 1 alpha (eEF1A) in vitro and in vivo.
Regulation of eukaryotic elongation factor 1 alpha (eEF1A) by dynamic lysine methylation
It is shown that lysine methylation of eEF1A can be dynamic and inducible, and modulates mRNA translation in a codon-specific fashion.
Saccharomyces cerevisiae Eukaryotic Elongation Factor 1A (eEF1A) Is Methylated at Lys-390 by a METTL21-Like Methyltransferase
The results demonstrate that Ynl024c is the enzyme responsible for methylation of eEF1A at Lys390, and in accordance with prior naming of similar enzymes, the YNL024c protein is suggested to be renamed to Efm6 (Elongation factor MTase 6).
Human METTL20 Is a Mitochondrial Lysine Methyltransferase That Targets the β Subunit of Electron Transfer Flavoprotein (ETFβ) and Modulates Its Activity*
The present study establishes METTL20 as the first human KMT localized to mitochondria and suggests that it may regulate cellular metabolism through modulating the interaction between its substrate ETFβ and dehydrogenases.
A Newly Uncovered Group of Distantly Related Lysine Methyltransferases Preferentially Interact with Molecular Chaperones to Regulate Their Activity
A new role for protein methylation as a regulatory pathway for molecular chaperones is uncovered and a novel regulatory mechanism for the chaperone VCP, whose deregulation is causative of degenerative neuromuscular diseases is defined.
NRMT is an α-N-methyltransferase that methylates RCC1 and Retinoblastoma Protein
The post-translational methylation of α-amino groups was first discovered over 30 years ago on the bacterial ribosomal proteins L16 and L33 (refs 1, 2), but almost nothing is known about the function