DAZL and CPEB1 regulate mRNA translation synergistically during oocyte maturation
DAZL and CPEB1 regulate mRNA translation synergistically during oocyte maturation
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DOI：
10.1242/jcs.179218
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发表时间：
2016-03-15
影响因子：
4
通讯作者：
Conti, Marco
中科院分区：
文献类型：
--
作者：
Martins, Joao P. Sousa;Liu, Xueqing;Conti, Marco
减数分裂的进行需要精巧地协调翻译在卵母细胞生长过程中积累的母体信使(M)RNA。该程序的一个主要调节因子是细胞质多聚腺苷酸化元件结合蛋白1(CPEB1)。然而，不同减数分裂阶段翻译的时间模式表明了额外的RNA结合蛋白(RBPs)的功能。在此，我们报道了类无精子症缺失基因(DAZL)与CPEB1协同调节母体mRNA的翻译。使用一种监测核糖体加载内源mRNAs的策略和一个原型翻译靶点，我们证明了当卵母细胞重新进入减数分裂时，核糖体加载是以DAZL和CPEB1依赖的方式诱导的。卵母细胞中两个限制性商业惯例的耗尽和3‘非翻译区(UTRs)的突变表明，这两个限制性商业惯例都与Tex19.1 3’非翻译区相互作用，并在该mRNA的翻译激活中协同作用。当使用全基因组分析时，我们观察到DAZL和细胞质多聚腺苷酸化元件(CPE)在母体mRNAs翻译模式中的协同作用。从机制上讲，DAZL蛋白的数量和CPE的性质可能决定了两个限制性商业惯例在激活翻译和减数分裂过程中的合作程度。
Meiotic progression requires exquisitely coordinated translation of maternal messenger (m) RNA that has accumulated during oocyte growth. A major regulator of this program is the cytoplasmic polyadenylation element binding protein 1 (CPEB1). However, the temporal pattern of translation at different meiotic stages indicates the function of additional RNA binding proteins (RBPs). Here, we report that deleted in azoospermia-like (DAZL) cooperates with CPEB1 to regulate maternal mRNA translation. Using a strategy that monitors ribosome loading onto endogenous mRNAs and a prototypic translation target, we show that ribosome loading is induced in a DAZL-and CPEB1-dependent manner, as the oocyte reenters meiosis. Depletion of the two RBPs from oocytes and mutagenesis of the 3' untranslated regions (UTRs) demonstrate that both RBPs interact with the Tex19.1 3' UTR and cooperate in translation activation of this mRNA. We observed a synergism between DAZL and cytoplasmic polyadenylation elements (CPEs) in the translation pattern of maternal mRNAs when using a genome-wide analysis. Mechanistically, the number of DAZL proteins loaded onto the mRNA and the characteristics of the CPE might define the degree of cooperation between the two RBPs in activating translation and meiotic progression.