P-body formation is a consequence, not the cause, of RNA-mediated gene silencing
P-body formation is a consequence, not the cause, of RNA-mediated gene silencing
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DOI：
10.1128/mcb.00128-07
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发表时间：
2007-06-01
影响因子：
5.3
通讯作者：
Izaurralde, Elisa
中科院分区：
文献类型：
--
作者：
Eulalio, Ana;Behm-Ansmant, Isabelle;Izaurralde, Elisa
P体是细胞质结构域，含有参与多种转录后过程的蛋白质，例如mRNA降解、无义介导的mRNA衰变(NMD)、翻译抑制和RNA介导的基因沉默。这些蛋白质及其靶标在 P 体中的定位提出了一个问题：转录后基因调控是否需要它们在离散细胞质结构域中的空间集中。我们证明，mRNA 衰变、NMD 和 RNA 介导的基因沉默等过程在缺乏可检测的微观 P 体的细胞中发挥作用。虽然沉默不需要 P 小体，但在任何步骤阻断小干扰 RNA 或 microRNA 沉默途径都会阻止 P 小体形成，表明 P 小体是沉默的结果。一致地，我们表明从多核糖体中释放 mRNA 不足以触发 P 体组装：无多核糖体的 mRNA 必须进入沉默和/或脱帽途径以使 P 体成核。因此，尽管 P 体成分在 mRNA 沉默和衰变中发挥着至关重要的作用，但聚集成 P 体并不是功能所必需的，而是其活性的结果。
P bodies are cytoplasmic domains that contain proteins involved in diverse posttranscriptional processes, such as mRNA degradation, nonsense-mediated mRNA decay (NMD), translational repression, and RNA-mediated gene silencing. The localization of these proteins and their targets in P bodies raises the question of whether their spatial concentration in discrete cytoplasmic domains is required for posttranscriptional gene regulation. We show that processes such as mRNA decay, NMD, and RNA-mediated gene silencing are functional in cells lacking detectable microscopic P bodies. Although P bodies are not required for silencing, blocking small interfering RNA or microRNA silencing pathways at any step prevents P-body formation, indicating that P bodies arise as a consequence of silencing. Consistently, we show that releasing mRNAs from polysomes is insufficient to trigger P-body assembly: polysome-free mRNAs must enter silencing and/or decapping pathways to nucleate P bodies. Thus, even though P-body components play crucial roles in mRNA silencing and decay, aggregation into P bodies is not required for function but is instead a consequence of their activity.