Asymmetric Arginine Dimethylation Determines Life Span in C. elegans by Regulating Forkhead Transcription Factor DAF-16

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 l...

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Bibliographic Details
Published in:Cell metabolism 2011-05, Vol.13 (5), p.505-516
Main Authors: 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
Format: Article
Language:English
Subjects:
AKT protein
Amino Acid Sequence
Animals
Arginine - genetics
Arginine - metabolism
Blotting, Western
Caenorhabditis elegans
Caenorhabditis elegans - genetics
Caenorhabditis elegans - growth & development
Caenorhabditis elegans - metabolism
Caenorhabditis elegans Proteins - genetics
Caenorhabditis elegans Proteins - metabolism
Forkhead Transcription Factors - genetics
Forkhead Transcription Factors - metabolism
Gene Expression Regulation
Immunoprecipitation
Insulin - genetics
Insulin - metabolism
Longevity - genetics
Methylation
Molecular Sequence Data
Mutation - genetics
Phosphorylation
Polymerase Chain Reaction
Protein-Arginine N-Methyltransferases - genetics
Protein-Arginine N-Methyltransferases - metabolism
Proto-Oncogene Proteins c-akt - genetics
Proto-Oncogene Proteins c-akt - metabolism
Receptor, Insulin - genetics
Receptor, Insulin - metabolism
Sequence Homology, Amino Acid
Signal Transduction
Transcription Factors - genetics
Transcription Factors - metabolism
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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. ► PRMT-1 is the predominant type I protein arginine methyltransferase in C. elegans ► PRMT-1 controls life span depending on both DAF-16 and its enzymatic activity ► PRMT-1 is also involved in stress tolerance and fat storage, but not dauer arrest ► PRMT-1-induced methylation of DAF-16 blocks its phosphorylation by AKT
ISSN:1550-4131
1932-7420
DOI:10.1016/j.cmet.2011.03.017