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

Eukaryotic elongation factor 1 alpha (eEF1A) delivers aminoacyl-tRNA to the ribosome and thereby plays a key role in protein synthesis. Human eEF1A is post-translationally methylated on several lysine residues as well as on the N-terminus and until recently the responsible methyltransferases were largely elusive. Using mass spectrometry based screens, gene targeted cells and in vitro enzymology we identify the human methyltransferase like proteins 13 (METTL13), which contains two distinct methyltransferase domains, as an enzyme catalyzing both dimethylation of Lys55 and trimethylation of the N-terminus of eEF1A. Moreover, through ribosome profiling we demonstrate that loss of METTL13 function alters translation dynamics and results in changed translation rate of specific codons. In line with the established descriptive nomenclature for this type of enzymes we suggest that METTL13 is redubbed eEF1A dual methyltransferase (eEF1A-DMT / EEF1ADMT). Overall design: ribosome profiling and poly(A) RNA sequencing of wildtype and MELL13-KO cells. Libraries were prepared as triplicates, except for wt ribosome profiling libraries that are duplicates only.