title: Methylation of ribosomal protein L42 regulates ribosomal function and stress-adapted cell growth.
abstract: Lysine methylation is one of the most common protein modifications. Although lysine methylation of histones has been extensively studied and linked to gene regulation, that of non-histone proteins remains incompletely understood. Here, we show a novel regulatory role of ribosomal protein methylation. Using an in vitro methyltransferase assay, we found that Schizosaccharomyces pombe Set13, a SET domain protein encoded by SPAC688.14, specifically methylates lysine 55 of ribosomal protein L42 (Rpl42). Mass spectrometric analysis revealed that endogenous Rpl42 is monomethylated at lysine 55 in wild-type S. pombe cells and that the methylation is lost in Delta set13 mutant cells. Delta set13 and Rpl42 methylation-deficient mutant S. pombe cells showed higher cycloheximide sensitivity and defects in stress-responsive growth control compared with wild type. Genetic analyses suggested that the abnormal growth phenotype was distinct from the conserved stress-responsive pathway that modulates translation initiation. Furthermore, the Rpl42 methylation-deficient mutant cells showed a reduced ability to survive after entering stationary phase. These results suggest that Rpl42 methylation plays direct roles in ribosomal function and cell proliferation control independently of the general stress-response pathway.
authors.affiliation: Laboratory for Chromatin Dynamics, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Shirai
authors.forename: Mahito
authors.initials: M
authors.lastname: Sadaie
authors.forename: Kaori
authors.initials: K
authors.lastname: Shinmyozu
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Nakayama
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects; D000595:Amino Acid Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000201:enzymology; D049109:Cell Proliferation / Q000187:drug effects; D002853:Chromatography, Liquid; D003080:Cold Temperature; D017124:Conserved Sequence; D003513:Cycloheximide / Q000633:toxicity; D006801:Humans; D008239:Lysine / Q000378:metabolism; D013058:Mass Spectrometry; D008745:Methylation / Q000187:drug effects; D008780:Methyltransferases / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D021381:Protein Transport / Q000187:drug effects; D011994:Recombinant Proteins / Q000378:metabolism; D012269:Ribosomal Proteins / Q000737:chemistry / Q000378:metabolism*; D054683:Ribosome Subunits, Large, Eukaryotic / Q000378:metabolism; D012270:Ribosomes / Q000187:drug effects / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000166:cytology / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000378:metabolism*; D013312:Stress, Physiological / Q000187:drug effects; D013997:Time Factors
chemical_list: C551256:RPl42 protein, S pombe; D011994:Recombinant Proteins; D012269:Ribosomal Proteins; D029702:Schizosaccharomyces pombe Proteins; D003513:Cycloheximide; D008780:Methyltransferases; D008239:Lysine
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