title: Asymmetric arginine dimethylation determines life span in C. elegans by regulating forkhead transcription factor DAF-16.
abstract: Arginine methylation is a widespread posttranslational modification of proteins catalyzed by a family of protein arginine methyltransferases (PRMTs). It is well established that PRMTs are implicated in various cellular processes, but their physiological roles remain unclear. Using nematodes with a loss-of-function mutation, we show that prmt-1, the major asymmetric arginine methyltransferase, is a positive regulator of longevity in C. elegans. This regulation is dependent on both its enzymatic activity and DAF-16/FoxO transcription factor, which is negatively regulated by AKT-mediated phosphorylation downstream of the DAF-2/insulin signaling. prmt-1 is also required for stress tolerance and fat storage but not dauer formation in daf-2 mutants. Biochemical analyses indicate that PRMT-1 methylates DAF-16, thereby blocking its phosphorylation by AKT. Disruption of PRMT-1 induces phosphorylation of DAF-16 with a concomitant reduction in the expression of longevity-related genes. Thus, we provide a mechanism by which asymmetric arginine dimethylation acts as an antiaging modification in C. elegans.
authors.affiliation: Life Science Center, Tsukuba Advanced Research Alliance, Graduate School of Life and Environmental Sciences, University of Tsukuba, Tennoudai, Ibaraki, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Daitoku
authors.forename: Keiko
authors.initials: K
authors.lastname: Hirota
authors.forename: Hiroko
authors.initials: H
authors.lastname: Tamiya
authors.forename: Atsuko
authors.initials: A
authors.lastname: Yokoyama
authors.forename: Koichiro
authors.initials: K
authors.lastname: Kako
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nagashima
authors.forename: Ayumi
authors.initials: A
authors.lastname: Nakamura
authors.forename: Takashi
authors.initials: T
authors.lastname: Shimada
authors.forename: Satoshi
authors.initials: S
authors.lastname: Watanabe
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Yamagata
authors.forename: Kayo
authors.initials: K
authors.lastname: Yasuda
authors.forename: Naoaki
authors.initials: N
authors.lastname: Ishii
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Fukamizu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D047468:Immunoprecipitation; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D008136:Longevity / Q000235:genetics*; D008745:Methylation; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D007328:Insulin; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; D001120:Arginine; D011484:Protein-Arginine N-Methyltransferases; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin; D051057:Proto-Oncogene Proteins c-akt