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

Autor:	Matsuura-Suzuki E; RNA Systems Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, Saitama, Japan., Shimazu T; Cellular Memory Laboratory, RIKEN Cluster for Pioneering Research, Saitama, Japan., Takahashi M; Laboratory for Translation Structural Biology, RIKEN Center for Biosystems Dynamics Research, Yokohama, Japan., Kotoshiba K; Cellular Memory Laboratory, RIKEN Cluster for Pioneering Research, Saitama, Japan., Suzuki T; Biomolecular Characterization Unit, Technology Platform Division, RIKEN Center for Sustainable Resource Science, Saitama, Japan., Kashiwagi K; Laboratory for Translation Structural Biology, RIKEN Center for Biosystems Dynamics Research, Yokohama, Japan., Sohtome Y; RIKEN Center for Sustainable Resource Science, Saitama, Japan.; Synthetic Organic Chemistry Lab, RIKEN Cluster for Pioneering Research, Saitama, Japan., Akakabe M; Synthetic Organic Chemistry Lab, RIKEN Cluster for Pioneering Research, Saitama, Japan., Sodeoka M; RIKEN Center for Sustainable Resource Science, Saitama, Japan.; Synthetic Organic Chemistry Lab, RIKEN Cluster for Pioneering Research, Saitama, Japan., Dohmae N; Biomolecular Characterization Unit, Technology Platform Division, RIKEN Center for Sustainable Resource Science, Saitama, Japan., Ito T; Laboratory for Translation Structural Biology, RIKEN Center for Biosystems Dynamics Research, Yokohama, Japan., Shinkai Y; Cellular Memory Laboratory, RIKEN Cluster for Pioneering Research, Saitama, Japan., Iwasaki S; RNA Systems Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, Saitama, Japan.; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2022 Jun 08; Vol. 11. Date of Electronic Publication: 2022 Jun 08.
DOI:	10.7554/eLife.72780
Abstrakt:	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 showed stoichiometric modification and suggested a role in translation reactions. Indeed, genome-wide ribosome profiling and an in vitro translation assay revealed that translation elongation at Tyr codons was suppressed by RPL3 methylation. Because the slower elongation provides enough time for nascent protein folding, RPL3 methylation protects cells from the cellular aggregation of Tyr-rich proteins. Our results reveal histidine methylation as an example of a ribosome modification that ensures proteome integrity in cells. Competing Interests: EM, TS, MT, KK, TS, KK, YS, MA, MS, ND, TI, YS, SI No competing interests declared
Databáze:	MEDLINE
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