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

Nucleic Acids Research
Magnus JakobssonPål Ø Falnes

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 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 act...Continue Reading

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Citations

Oct 5, 2017·Nucleic Acids Research·Audrey M MichelPavel V Baranov
Jun 23, 2018·Journal of Experimental Botany·Nelson B C SerreStéphane Ravanel
Feb 16, 2018·RNA Biology·Magnus E JakobssonPål Ø Falnes
Aug 21, 2019·Journal of the American Society for Mass Spectrometry·Xin YanChenxi Jia
Jul 24, 2020·Molecular Biology and Evolution·Samantha J Emery-CorbinAaron R Jex
Jul 3, 2020·The Journal of Biological Chemistry·Muhammad ZoabiOr Gozani
Dec 12, 2018·The Journal of Biological Chemistry·Jędrzej M MałeckiPål Ø Falnes
Jan 21, 2021·Nature Reviews. Drug Discovery·Kamakoti P BhatOr Gozani
Feb 2, 2021·Frontiers in Molecular Biosciences·Taku KaitsukaMasayuki Matsushita
May 12, 2021·Cellular Signalling·Lilas AlboushiSeyed Mehdi Jafarnejad
May 29, 2021·NAR Genomics and Bioinformatics·Sebastian Kapell, Magnus E Jakobsson
Jan 3, 2020·Current Protein & Peptide Science·Valentina LukinovićNicolas Reynoird
Aug 31, 2021·The Journal of Biological Chemistry·Magnus E Jakobsson

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Datasets Mentioned

BETA
GSE97140

Methods Mentioned

BETA
PCR
tandem affinity purification
transfection
electrophoresis
scraping
proteomic profiling
protein
aminoacylation
footprinting
ubiquitination

Software Mentioned

Ensembl
. fr
DESeq2 R - package
UCSC genome browser
METTL18
PyMOL Molecular Graphics System
GOrilla
phylogeny
Jalview
Qual Browser

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