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

Jakobsson, Magnus E LU ; Małecki, Jędrzej M ; Halabelian, Levon ; Nilges, Benedikt S ; Pinto, Rita ; Kudithipudi, Srikanth ; Munk, Stephanie ; Davydova, Erna ; Zuhairi, Fawzi R and Arrowsmith, Cheryl H , et al. (2018) In Nature Communications 9(1). p.3411-3411
Abstract

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 structural analyses provide detailed mechanistic insights into recognition of the eEF1A N terminus by METTL13. Moreover, through ribosome profiling, we demonstrate that loss of METTL13 function alters translation dynamics and results in changed... (More)

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 structural analyses provide detailed mechanistic insights into recognition of the eEF1A N terminus by METTL13. Moreover, through ribosome profiling, we demonstrate that loss of METTL13 function alters translation dynamics and results in changed translation rates of specific codons. In summary, we here unravel the function of a human MTase, showing that it methylates eEF1A and modulates mRNA translation in a codon-specific manner.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Codon/genetics, Humans, Methyltransferases/chemistry, Peptide Elongation Factor 1/chemistry, Protein Binding, Protein Processing, Post-Translational, RNA, Messenger/metabolism, Ribosomes/metabolism
in
Nature Communications
volume
9
issue
1
pages
3411 - 3411
publisher
Nature Publishing Group
external identifiers
  • scopus:85052383859
  • pmid:30143613
ISSN
2041-1723
DOI
10.1038/s41467-018-05646-y
language
English
LU publication?
no
id
ea4e583d-9ab5-4282-b7fe-0a85ca7defb9
date added to LUP
2020-01-13 08:51:23
date last changed
2024-05-16 03:57:33
@article{ea4e583d-9ab5-4282-b7fe-0a85ca7defb9,
  abstract     = {{<p>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 structural analyses provide detailed mechanistic insights into recognition of the eEF1A N terminus by METTL13. Moreover, through ribosome profiling, we demonstrate that loss of METTL13 function alters translation dynamics and results in changed translation rates of specific codons. In summary, we here unravel the function of a human MTase, showing that it methylates eEF1A and modulates mRNA translation in a codon-specific manner.</p>}},
  author       = {{Jakobsson, Magnus E and Małecki, Jędrzej M and Halabelian, Levon and Nilges, Benedikt S and Pinto, Rita and Kudithipudi, Srikanth and Munk, Stephanie and Davydova, Erna and Zuhairi, Fawzi R and Arrowsmith, Cheryl H and Jeltsch, Albert and Leidel, Sebastian A and Olsen, Jesper V and Falnes, Pål Ø}},
  issn         = {{2041-1723}},
  keywords     = {{Codon/genetics; Humans; Methyltransferases/chemistry; Peptide Elongation Factor 1/chemistry; Protein Binding; Protein Processing, Post-Translational; RNA, Messenger/metabolism; Ribosomes/metabolism}},
  language     = {{eng}},
  month        = {{08}},
  number       = {{1}},
  pages        = {{3411--3411}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{The dual methyltransferase METTL13 targets N terminus and Lys55 of eEF1A and modulates codon-specific translation rates}},
  url          = {{http://dx.doi.org/10.1038/s41467-018-05646-y}},
  doi          = {{10.1038/s41467-018-05646-y}},
  volume       = {{9}},
  year         = {{2018}},
}