A requirement for ERK-dependent Dicer phosphorylation in coordinating oocyte-to-embryo transition in C. elegans.

A requirement for ERK-dependent Dicer phosphorylation in coordinating oocyte-to-embryo transition in C. elegans.
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DOI:
10.1016/j.devcel.2014.11.004
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发表时间:
2014-12-08
期刊:
影响因子:
11.8
通讯作者:
Arur, Swathi
Arur, Swathi
中科院分区:
生物学1区
文献类型:
--
作者:
Drake, Melanie;Furuta, Tokiko;Suen, Kin Man;Gonzalez, Gabriel;Liu, Bin;Kalia, Awdhesh;Ladbury, John E.;Fire, Andrew Z.;Skeath, James B.;Arur, Swathi

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信号通路和小RNA指导不同的细胞事件,但很少有明确的信号通路直接调节小RNA生物合成的例子。我们表明,ERK磷酸化Dicer的两个保守残基在其RNAse IIIb和dsRNA结合域,这些残基的磷酸化是必要的,足以触发Dicer的核转位蠕虫,小鼠和人类细胞。Dicer在任一位点上的磷酸化抑制Dicer在雌性生殖系中的功能并抑制小RNA库。我们的数据表明,ERK磷酸化和抑制Dicer在减数分裂I卵子发生正常进行在C。这种抑制作用在受精前被释放,胚胎发生才能正常进行。保守的Dicer残基,其磷酸化的ERK,以及由此产生的修改的后果牵连的ERK-Dicer连接作为卵母细胞到胚胎过渡的基本组成部分和耦合细胞外的线索小RNA的生产的潜在机制。
Signaling pathways and small RNAs direct diverse cellular events, but few examples are known of defined signaling pathways directly regulating small RNA biogenesis. We show that ERK phosphorylates Dicer on two conserved residues in its RNAse IIIb and dsRNA-binding domain, and phosphorylation of these residues is necessary and sufficient to trigger Dicer’s nuclear translocation in worms, mice, and human cells. Phosphorylation of Dicer on either site inhibits Dicer function in the female germ line and dampens small RNA repertoire. Our data demonstrate that ERK phosphorylates and inhibits Dicer during meiosis I for oogenesis to proceed normally in C. elegans and that this inhibition is released before fertilization for embryogenesis to proceed normally. The conserved Dicer residues, their phosphorylation by ERK, and the consequences of the resulting modifications implicate an ERK-Dicer nexus as a fundamental component of the oocyte-to-embryo transition and an underlying mechanism coupling extracellular cues to small RNA production.
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