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Adenylation of maternally inherited microRNAs by Wispy
Mihye Lee1, Yeon Choi1, Kijun Kim1
1Center for RNA Research, Institute for Basic Science, Seoul 151-742, Korea; School of Biological Sciences, Seoul National University, Seoul 151-742, Korea.
Abstract:
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.
Insights
Maternal microRNAs are adenylated in eggs and early embryos, a process conserved across species. This adenylation, mediated by Wispy (a poly(A) polymerase), helps clear maternal microRNAs during development.
Area of Science:
- Developmental Biology
- RNA Biology
- Molecular Genetics
Background:
- Accurate control of maternal transcripts is crucial for early development.
- Mechanisms regulating maternal microRNAs during the maternal-to-zygotic transition (MZT) are largely unknown.
Purpose of the Study:
- To investigate the regulation of maternal microRNAs during MZT.
- To identify the molecular players involved in maternal microRNA regulation.
Main Methods:
- Analysis of microRNA adenylation in oocytes and early embryos across species (fly, sea urchin, mouse).
- Genetic manipulation of Wispy (a poly(A) polymerase) in Drosophila.
- Investigation of Wispy-Ago1 protein interactions.
Main Results:
- Maternal microRNAs are extensively adenylated at their 3' ends in oocytes and early embryos.
- Wispy is identified as the enzyme responsible for microRNA adenylation in flies.
- Wispy knockout leads to microRNA accumulation, while overexpression reduces microRNA levels.
- Wispy interacts with Ago1, suggesting a mechanism for selective microRNA targeting.
Conclusions:
- MicroRNA adenylation, mediated by Wispy, contributes to the clearance of maternal microRNAs during MZT.
- RNA tailing plays a significant role in the regulation of maternal microRNAs and early development.
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