Functionally distinct roles for eEF2K in the control of ribosome availability and p-body abundance.
Functionally distinct roles for eEF2K in the control of ribosome availability and p-body abundance.
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DOI：
10.1038/s41467-021-27160-4
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发表时间：
2021-11-23
影响因子：
16.6
通讯作者：
Campbell ZT
中科院分区：
文献类型：
--
作者：
Smith PR;Loerch S;Kunder N;Stanowick AD;Lou TF;Campbell ZT
加工体（p-bodies）是一种典型的相分离的含RNA颗粒。它们的丰富是高度动态的，并与翻译有关。然而，负责协调控制这两个过程的分子机制尚不清楚。在这里，我们揭示了eEF 2激酶（eEF 2K）在控制核糖体可用性和p体丰度中的关键作用。eEF 2K作用于唯一已知的底物eEF 2以抑制翻译。我们发现，eEF 2K激动剂奈非那韦废除感觉神经元中的p-小体，并损害翻译。为了探测后者，我们使用冷冻电子显微镜。奈非那韦稳定空的80 S核糖体。它们在受体位点含有代替mRNA的SERBP 1和eEF 2。磷酸化的eEF 2与在体外抵抗分裂的无活性核糖体相关联。总的来说，这些数据表明eEF 2K定义了一群不活跃的核糖体，这些核糖体抵抗再循环并被保护免于降解。因此，eEF 2K活性是感觉神经元中p体丰度和核糖体可用性的核心。加工体是富含抑制mRNA的相分离区室。在这里，Smith等人表明，在感觉神经元中，真核细胞延伸因子2激酶（eEF 2K）在调节加工体丰度和形成无活性核糖体中起关键作用。
Processing bodies (p-bodies) are a prototypical phase-separated RNA-containing granule. Their abundance is highly dynamic and has been linked to translation. Yet, the molecular mechanisms responsible for coordinate control of the two processes are unclear. Here, we uncover key roles for eEF2 kinase (eEF2K) in the control of ribosome availability and p-body abundance. eEF2K acts on a sole known substrate, eEF2, to inhibit translation. We find that the eEF2K agonist nelfinavir abolishes p-bodies in sensory neurons and impairs translation. To probe the latter, we used cryo-electron microscopy. Nelfinavir stabilizes vacant 80S ribosomes. They contain SERBP1 in place of mRNA and eEF2 in the acceptor site. Phosphorylated eEF2 associates with inactive ribosomes that resist splitting in vitro. Collectively, the data suggest that eEF2K defines a population of inactive ribosomes resistant to recycling and protected from degradation. Thus, eEF2K activity is central to both p-body abundance and ribosome availability in sensory neurons. Processing bodies are phase separated compartments enriched in translationally repressed mRNAs. Here, Smith et al. show that, in sensory neurons, eukaryotic elongation factor 2 kinase (eEF2K) plays key roles in the regulation of processing body abundance and the formation of translationally inactive ribosomes.
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影响因子：
64.8
作者：
Autry, Anita E.;Adachi, Megunai;Nosyreva, Elena;Na, Elisa S.;Los, Maarten F.;Cheng, Peng-fei;Kavalali, Ege T.;Monteggia, Lisa M.
通讯作者：
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影响因子：
64.5
作者：
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影响因子：
5.2
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影响因子：
3.3
作者：
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通讯作者：
Weil D
影响因子：
16
作者：
Arribere, Joshua A.;Doudna, Jennifer A.;Gilbert, Wendy V.
通讯作者：
Gilbert, Wendy V.