TY - JOUR T1 - Asymmetric arginine dimethylation determines life span in C. elegans by regulating forkhead transcription factor DAF-16. AU - Takahashi,Yuta, AU - Daitoku,Hiroaki, AU - Hirota,Keiko, AU - Tamiya,Hiroko, AU - Yokoyama,Atsuko, AU - Kako,Koichiro, AU - Nagashima,Yusuke, AU - Nakamura,Ayumi, AU - Shimada,Takashi, AU - Watanabe,Satoshi, AU - Yamagata,Kazuyuki, AU - Yasuda,Kayo, AU - Ishii,Naoaki, AU - Fukamizu,Akiyoshi, PY - 2010/08/26/received PY - 2011/01/20/revised PY - 2011/03/17/accepted PY - 2011/5/3/entrez PY - 2011/5/3/pubmed PY - 2011/9/6/medline SP - 505 EP - 16 JF - Cell metabolism JO - Cell Metab VL - 13 IS - 5 N2 - 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. SN - 1932-7420 UR - https://www.unboundmedicine.com/medline/citation/21531333/Asymmetric_arginine_dimethylation_determines_life_span_in_C__elegans_by_regulating_forkhead_transcription_factor_DAF_16_ DB - PRIME DP - Unbound Medicine ER -