| The regulation of life span is one of the important fields for studying the mechanisms of aging regulation. C. elegans is an important model in life span regulation, because it is easy to raise and it has short life cycle and completed genome sequencing. In recent years, some evidences have shown that the post-translational modification of proteins plays an important role in the lifespan regulation. Protein post-translational modifications include methylation, acetylation, phosphorylation, and so on. It has been known that transcription factor DAF-16 and SKN-1 regulate lifespan mainly through the phosphorylation by controlling their translocation to the nuclei. In addition, enhancing histone deacetylase SIR-2.1 expression levels can prolong the lifespan of C. elegans. The O-Glc NAc glycosylation regulates lifespan by Insulin-PI3K-AKT signaling pathway. Lysine methylation has also been found to been involved in the regulation of lifespan. Inhibition of the activity of histone H3K27 demethylase UTX-1increased the level of histone H3K27 on DAF-2 promter, which down-regulated the expression of DAF-2. The decrease of DAF-2 expression facilitated the translocation of DAF-16 into the nucleus and extended the lifespan of C.elegans.Arginine methylation is one kind of methylation modifications. Now, there are six arginine methyltransferases discovered in C. elegans, PRMT-1,-2,-3,-4,-5,-6. It has been reported that PRMT-1 is closely related to the regulation of lifespan in C. elegans. PRMT-1 methylated DAF-16, the key transcription factor of IIS signaling pathway, and inhibited the phosphorylation of DAF-16 by protein kinase AKT, which promoted the accumulation of DAF-16 in the nucleus, increased the target gene expressions of sod-3 and sip-1, and prolonged the lifespan.According to our previous study, arginine methyltransferase PRMT-6 can influence the lifespan of C. elegans. The life span of prmt-6 mutants were longer than wide type N2. In addition, we found that PRMT-6 regulated the life span, depending on SKN-1, but not DAF-16. However, it is still unclear how PRMT-6 regulates the life span in C. elegans by SKN-1.SKN-1 is a transcription factor in IIS signaling pathway. it plays an important role in embryonic development. During the early stage of embryonic development, SKN-1 directly influenced the differentiation and development of the E cells and MS cells in the EMS blastomeres. During the stage of EMS blastomeres, SKN-1 induced the zinc finger protein MED-1 and MED-2 expression, and induced the defective of throat and intestine development. After the embryonic development, SKN-1 regulated the response of oxide stress and life span by the accumulation in nucleus of intestine and activation the expression of SKN-1’s target genes through many pathways, such as MAPK signaling pathway, Insulin/IGF-1(IIS) signaling pathway, and rapamycin(TOC) signaling pathway.In order to study how the arginine methyltransferase PRMT-6 regulated the lifespan of C. elegans by SKN-1, we first used RNAi to confirm further that PRMT-6 regulated the lifespan of C. elegans by SKN-1. Then, according to genetic analysis, the skn-1 gene with GFP tag was integrated into the genome of prmt-6 mutants. Next, we checked the accumulation of SKN-1 in intestinal cell nucleus by the laser scanning confocal microscope, and found that PRMT-6 inhibited the SKN-1 accumulation in nucleus of intestine. At last, we tested the m RNA expression levels of SKN-1 target genes gcs-1, gst-4 and gst-10 in prmt-6 mutants and wide type N2 by RT-PCR. It was found that the expression levels of three target genes in prmt-6 mutants were all higher than those of N2. These data indicated that PRMT-6 prevented SKN-1 accumulation in nucleus of intestine and the target gene expression level to regulate the lifespan. These results laid a foundation for the further research of PRMT-6 molecular mechanisms involved in the regulation of aging. |
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