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

Nature Communications
Magnus E JakobssonPål Ø Falnes

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 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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Citations

Sep 5, 2018·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Yan LiAtsushi Takahashi
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Aug 13, 2021·Journal of Proteome Research·Panyue ChenTony R Hazbun

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Datasets Mentioned

BETA
GSE104033
PXD008115
PXD008131
PXD009895
PXD009914

Methods Mentioned

BETA
acetylation
pull-down
pull-downs
peptide array
nucleotide exchange
PCR
scraping
Protein Assay
size exclusion chromatography
density gradient fractionator

Software Mentioned

REFMAC
R
Perseus
XDS
MaxQuant
Ligprep
ConSurf
COOT
Perl
Xcalibur Qual Browser

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