Center for RNA Research, Institute for Basic Science, Seoul 151-742, Korea; School of Biological Sciences, Seoul National University, Seoul 151-742, Korea.
Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT 06520, USA.
Mol Cell. 2014 Dec 4;56(5):696-707. doi: 10.1016/j.molcel.2014.10.011. Epub 2014 Nov 13.
Early development depends heavily on accurate control of maternally inherited mRNAs, and yet it remains unknown how maternal microRNAs are regulated during maternal-to-zygotic transition (MZT). We here find that maternal microRNAs are highly adenylated at their 3' ends in mature oocytes and early embryos. Maternal microRNA adenylation is widely conserved in fly, sea urchin, and mouse. We identify Wispy, a noncanonical poly(A) polymerase, as the enzyme responsible for microRNA adenylation in flies. Knockout of wispy abrogates adenylation and results in microRNA accumulation in eggs, whereas overexpression of Wispy increases adenylation and reduces microRNA levels in S2 cells. Wispy interacts with Ago1 through protein-protein interaction, which may allow the effective and selective adenylation of microRNAs. Thus, adenylation may contribute to the clearance of maternally deposited microRNAs during MZT. Our work provides mechanistic insights into the regulation of maternal microRNAs and illustrates the importance of RNA tailing in development.
早期发育在很大程度上依赖于母体遗传 mRNA 的精确控制，但目前尚不清楚母体 microRNA 在母源到合子过渡（MZT）期间是如何被调控的。我们在这里发现，成熟卵母细胞和早期胚胎中的母体 microRNA 在其 3' 末端高度腺苷酸化。母体 microRNA 的腺苷酸化在果蝇、海胆和小鼠中广泛保守。我们鉴定出 Wispy 是一种非典型的 poly(A) 聚合酶，是果蝇中 microRNA 腺苷酸化的酶。wispy 的敲除会破坏腺苷酸化，导致卵母细胞中 microRNA 的积累，而 Wispy 的过表达会增加腺苷酸化并降低 S2 细胞中的 microRNA 水平。Wispy 通过蛋白-蛋白相互作用与 Ago1 相互作用，这可能允许 microRNA 的有效和选择性腺苷酸化。因此，腺苷酸化可能有助于在 MZT 期间清除母体沉积的 microRNA。我们的工作为母体 microRNA 的调控提供了机制上的见解，并说明了 RNA 尾部在发育中的重要性。
