Keiko HIROTA    Department   School of Medicine, School of Medicine    Position   Assistant Professor
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	Asymmetric arginine dimethylation determines lifespan in C. elegans by regulating forkhead transcription factor DAF-16
Journal	Formal name：Cell metabolism Abbreviation：Cell Metab ISSN code：15504131
Domestic / Foregin	Foregin
Volume, Issue, Page	13(5),pp.505-516
Author and coauthor	TAKAHASHI Yuta†, DAITOKU Hiroaki, HIROTA Keiko, TAMIYA Hiroko, YOKOYAMA Atsuko, KAKO Koichiro, NAGASHIMA Yusuke, NAKAMURA Ayumi, SHIMADA Takashi, WATANABE Satoshi, YAMAGATA Kazuyuki, YASUDA Kayo, ISHII Naoaki, FUKAMIZU Akiyoshi*
Publication date	2011/05
Summary	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.
DOI	10.1016/j.cmet.2011.03.017.