Methylation of human eukaryotic elongation factor alpha (eEF1A) by a member of a novel protein lysine methyltransferase family modulates mRNA translation
Autor: | Pål Ø. Falnes, Benedikt S. Nilges, Jędrzej Małecki, Anders Moen, Magnus E. Jakobsson, Sebastian A. Leidel |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Eukaryotic Initiation Factor-1 Biology Methylation Histone-Lysine N-Methyltransferase Cell Line Gene Knockout Techniques 03 medical and health sciences Eukaryotic translation Genetics Humans Amino Acid Sequence RNA Messenger Phylogeny Base Sequence Sequence Homology Amino Acid Lysine Gene regulation Chromatin and Epigenetics Translation (biology) Methyltransferases Eukaryotic translation elongation factor 1 alpha 1 Elongation factor 030104 developmental biology Biochemistry Protein Biosynthesis Histone methyltransferase Electrophoresis Polyacrylamide Gel Sequence motif |
Zdroj: | Nucleic Acids Research |
ISSN: | 1362-4962 0305-1048 |
Popis: | 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. |
Databáze: | OpenAIRE |
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