METTL18-mediated histidine methylation of RPL3 modulates translation elongation for proteostasis maintenance.

ABSTRACT: Protein methylation occurs predominantly on lysine and arginine residues, but histidine also serves as a methylation substrate. However, a limited number of enzymes responsible for this modification have been reported. Moreover, the biological role of histidine methylation has remained poorly understood to date. Here, we report that human METTL18 is a histidine methyltransferase for the ribosomal protein RPL3 and that the modification specifically slows ribosome traversal on Tyr codons, allowing the proper folding of synthesized proteins. By performing an in vitro methylation assay with a methyl donor analog and quantitative mass spectrometry, we found that His245 of RPL3 is methylated at the τ-N position by METTL18. Structural comparison of the modified and unmodified ribosomes sho

SUBMITTER: Matsuura-Suzuki E 

PROVIDER: S-EPMC9177149 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature