卵母細胞における染色体ダイナミクス制御と母体の加齢効果

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The highly conserved Serine/Threonine protein phosphatase PP4 homolog, PPH-4.1 in C. elegans, is required to regulate meiosis. The pph-4.1 null mutants Δ pph-4.1 show very low fecundity. The goal of our project is to identify the interactors of PPH-4.1, furthermore, to understand the molecular mechanisms of how PPH-4.1 regulate the fecundity of worms. We performed genetic screen to look for PPH-4.1 interactors, potentially its suppressors. Overall, 10470 genomes were screened and 73 potential pph-4.1 suppressor strains were isolated. After whole genome sequencing analysis, we found there is a mutation causing dct-17 coding sequence changed. To dampen the function of DCT-17, we also used RNA interference (RNAi) method to resemble EMS introduced dct-17 mutation. Our RNAi experiement showed consistent results, reduction of dct-17 mRNA by RNAi bacteria feeding to Δ pph-4.1 mutants dramatically improve the fecundity of the mutants. This result indicate dct-17 might be pph-4.1’s suppressor in regulating meiosis. DCT-17 is a predicted pyrophosphatase. Pyrophosphatase is an enzyme that catalyzes the conversion of one molecule of pyrophosphate to two phosphate ions. In Δ pph-4.1 mutants, PPH-4.1’s substrates are hyperphosphorylated, resulting in very low fecundity. Our result suggested dampening the function of dct-17 resulted in the reduction of the total phosphate, thereby, change the requirement of phosphorylation events during meiosis, leading to improvement of the fecundity in pph-4.1 null mutants. Our result might also shed light on how to improve human’s fecundity.