4.5 Article

Protein Arginine Methyltransferase 5 Is Necessary for Embryonic Development in Medaka Oryzias latipes

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FISHES
卷 8, 期 1, 页码 -

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MDPI
DOI: 10.3390/fishes8010019

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medaka; prmt5; gene editing; embryonic development; gene expression; stemness; apoptosis

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Prmt5 is an enzyme that catalyzes arginine dimethylation in proteins and is conserved from yeast to humans. It is necessary for embryonic development in mice and maintains embryonic stem cells. However, the knockout of prmt5 in zebrafish does not affect the viability of the embryos, suggesting that prmt5 may be dispensable during embryogenesis in fish. In this study using medaka, a different fish organism, the mutation of prmt5 resulted in down-regulation of stemness genes and up-regulation of genes associated with cell death, indicating that prmt5 is necessary for embryogenesis in medaka by maintaining stemness and repressing apoptosis.
Protein arginine methyltransferase 5 (Prmt5), conserved from yeast to humans, catalyzes arginine's dimethylation in proteins. Prmt5 is necessary for embryonic development in mice because it maintains embryonic stem cells. However, the embryos of zebrafish (Danio rerio) remain viable with a deficiency in germ cells and sexual development after the knockout of prmt5. Therefore, it was considered whether prmt5 is dispensable during embryogenesis in fish. Medaka (Oryzias latipes), another model fish organism, was used in this experiment. The medaka prmt5 was mutated with Transcription Activator-Like Effector Nucleases (TALEN) causing the premature stopping of transcription. None of the homozygous prmt5 mutant fish were viable, only the heterozygous offspring survived. Quantitative reverse transcription-polymerase chain reaction (qPCR) results showed a significant decrease in octamer-binding transcription factor 4 (oct4), homeobox transcription factor nanog (nanog), vasa, B-cell CLL/lymphoma 2 (bcl2), and the ratio of bcl2 to bax (bcl2 associated x), and a significant increase in caspase3 and caspase8 in the embryos of the heterozygous prmt5 mutant compared with that of the wild type. The results showed that the mutation of prmt5 caused down-regulation of the genes functioning in stemness and up-regulation of the genes in the cascade of cell death. These results suggested that prmt5 is necessary for embryogenesis via maintaining stemness and repressing apoptosis in medaka.

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