Stage-specific combinations of opposing poly(A) modifying enzymes guide gene expression during early oogenesis
Stage-specific combinations of opposing poly(A) modifying enzymes guide gene expression during early oogenesis
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DOI：
10.1093/nar/gkz787
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发表时间：
2019-09
影响因子：
14.9
通讯作者：
Marco Nousch;Assa Yeroslaviz;C. Eckmann
中科院分区：
文献类型：
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作者：
Marco Nousch;Assa Yeroslaviz;C. Eckmann
摘要针对mRNA poly（A）尾的RNA修饰酶是转录后基因表达程序的通用调节因子。目前的数据表明，RNA结合蛋白（RBP）指导拔河之间的尾巴缩短和再延长酶在细胞质中运作，以抑制或激活特定的mRNA靶。虽然这一概念被广泛接受，但它主要是在青蛙卵子发生的最后减数分裂阶段描述的，并且在分子上依赖于单一类别的RBP，即CPEB，去腺苷酸酶PARN和细胞质poly（A）聚合酶GLD-2。利用线虫雌配子发生的空间和时间分辨率。在线虫中，我们确定了已知的去腺苷酸酶在整个生殖细胞发育过程中的不同作用，并发现Ccr 4-Not复合物是GLD-2介导的mRNA调控的主要拮抗剂。我们发现，Ccr 4-Not/GLD-2平衡是至关重要的卵母细胞生产的基本上所有步骤和粘附地采用各种类型的RBP。有趣的是，它的两个deadenylase亚基似乎影响mRNA阶段具体：而Caf 1/GLD-2拮抗作用调节mRNA丰度在卵母细胞生产的所有阶段，Ccr 4/GLD-2拮抗作用调节卵子发生在mRNA丰度独立的方式。我们的综合数据表明，Ccr 4-Not复合物代表了GLD-2的进化保守分子对手，提供了基因特异性poly（A）-尾调控的拮抗框架。
Abstract RNA-modifying enzymes targeting mRNA poly(A) tails are universal regulators of post-transcriptional gene expression programs. Current data suggest that an RNA-binding protein (RBP) directed tug-of-war between tail shortening and re-elongating enzymes operates in the cytoplasm to repress or activate specific mRNA targets. While this concept is widely accepted, it was primarily described in the final meiotic stages of frog oogenesis and relies molecularly on a single class of RBPs, i.e. CPEBs, the deadenylase PARN and cytoplasmic poly(A) polymerase GLD-2. Using the spatial and temporal resolution of female gametogenesis in the nematode C. elegans, we determined the distinct roles of known deadenylases throughout germ cell development and discovered that the Ccr4–Not complex is the main antagonist to GLD-2-mediated mRNA regulation. We find that the Ccr4–Not/GLD-2 balance is critical for essentially all steps of oocyte production and reiteratively employed by various classes of RBPs. Interestingly, its two deadenylase subunits appear to affect mRNAs stage specifically: while a Caf1/GLD-2 antagonism regulates mRNA abundance during all stages of oocyte production, a Ccr4/GLD-2 antagonism regulates oogenesis in an mRNA abundance independent manner. Our combined data suggests that the Ccr4–Not complex represents the evolutionarily conserved molecular opponent to GLD-2 providing an antagonistic framework of gene-specific poly(A)-tail regulation.