Advanced

Methylation of human eukaryotic elongation factor alpha (eEF1A) by a member of a novel protein lysine methyltransferase family modulates mRNA translation

Jakobsson, Magnus E LU ; Malecki, Jedrzej ; Nilges, Benedikt S ; Moen, Anders ; Leidel, Sebastian A and Falnes, Pål Ø (2017) In Nucleic Acids Research 45(14). p.8239-8254
Abstract

Many cellular proteins are methylated on lysine residues and this has been most intensively studied for histone proteins. Lysine methylations on non-histone proteins are also frequent, but in most cases the functional significance of the methylation event, as well as the identity of the responsible lysine (K) specific methyltransferase (KMT), remain unknown. Several recently discovered KMTs belong to the so-called seven-β-strand (7BS) class of MTases and we have here investigated an uncharacterized human 7BS MTase currently annotated as part of the endothelin converting enzyme 2, but which should be considered a separate enzyme. Combining in vitro enzymology and analyzes of knockout cells, we demonstrate that this MTase efficiently... (More)

Many cellular proteins are methylated on lysine residues and this has been most intensively studied for histone proteins. Lysine methylations on non-histone proteins are also frequent, but in most cases the functional significance of the methylation event, as well as the identity of the responsible lysine (K) specific methyltransferase (KMT), remain unknown. Several recently discovered KMTs belong to the so-called seven-β-strand (7BS) class of MTases and we have here investigated an uncharacterized human 7BS MTase currently annotated as part of the endothelin converting enzyme 2, but which should be considered a separate enzyme. Combining in vitro enzymology and analyzes of knockout cells, we demonstrate that this MTase efficiently methylates K36 in eukaryotic translation elongation factor 1 alpha (eEF1A) in vitro and in vivo. We suggest that this novel KMT is named eEF1A-KMT4 (gene name EEF1AKMT4), in agreement with the recently established nomenclature. Furthermore, by ribosome profiling we show that the absence of K36 methylation affects translation dynamics and changes translation speed of distinct codons. Finally, we show that eEF1A-KMT4 is part of a novel family of human KMTs, defined by a shared sequence motif in the active site and we demonstrate the importance of this motif for catalytic activity.

(Less)
Please use this url to cite or link to this publication:
author
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Amino Acid Sequence, Base Sequence, Cell Line, Electrophoresis, Polyacrylamide Gel, Eukaryotic Initiation Factor-1/genetics, Gene Knockout Techniques, Histone-Lysine N-Methyltransferase, Humans, Lysine/genetics, Methylation, Methyltransferases/genetics, Phylogeny, Protein Biosynthesis, RNA, Messenger/genetics, Sequence Homology, Amino Acid
in
Nucleic Acids Research
volume
45
issue
14
pages
16 pages
publisher
Oxford University Press
external identifiers
  • scopus:85031853735
  • pmid:28520920
ISSN
1362-4962
DOI
10.1093/nar/gkx432
language
English
LU publication?
no
additional info
© The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.
id
4e04168d-4698-4d74-b47b-d9e9d942942c
date added to LUP
2020-01-13 08:53:35
date last changed
2020-05-26 05:38:09
@article{4e04168d-4698-4d74-b47b-d9e9d942942c,
  abstract     = {<p>Many cellular proteins are methylated on lysine residues and this has been most intensively studied for histone proteins. Lysine methylations on non-histone proteins are also frequent, but in most cases the functional significance of the methylation event, as well as the identity of the responsible lysine (K) specific methyltransferase (KMT), remain unknown. Several recently discovered KMTs belong to the so-called seven-β-strand (7BS) class of MTases and we have here investigated an uncharacterized human 7BS MTase currently annotated as part of the endothelin converting enzyme 2, but which should be considered a separate enzyme. Combining in vitro enzymology and analyzes of knockout cells, we demonstrate that this MTase efficiently methylates K36 in eukaryotic translation elongation factor 1 alpha (eEF1A) in vitro and in vivo. We suggest that this novel KMT is named eEF1A-KMT4 (gene name EEF1AKMT4), in agreement with the recently established nomenclature. Furthermore, by ribosome profiling we show that the absence of K36 methylation affects translation dynamics and changes translation speed of distinct codons. Finally, we show that eEF1A-KMT4 is part of a novel family of human KMTs, defined by a shared sequence motif in the active site and we demonstrate the importance of this motif for catalytic activity.</p>},
  author       = {Jakobsson, Magnus E and Malecki, Jedrzej and Nilges, Benedikt S and Moen, Anders and Leidel, Sebastian A and Falnes, Pål Ø},
  issn         = {1362-4962},
  language     = {eng},
  month        = {08},
  number       = {14},
  pages        = {8239--8254},
  publisher    = {Oxford University Press},
  series       = {Nucleic Acids Research},
  title        = {Methylation of human eukaryotic elongation factor alpha (eEF1A) by a member of a novel protein lysine methyltransferase family modulates mRNA translation},
  url          = {http://dx.doi.org/10.1093/nar/gkx432},
  doi          = {10.1093/nar/gkx432},
  volume       = {45},
  year         = {2017},
}