小柯机器人

近日，奥地利分子病理学研究所Andrea Pauli等研究人员合作发现，保守因子的分子网络使核糖体在卵子中处于休眠状态。相关论文于2023年1月18日在线发表在《自然》杂志上。

对从斑马鱼（Danio rerio）和爪蟾（Xenopthem laevis）卵和胚胎分离的核糖体进行质谱和冷冻电镜分析，研究人员提供了在胚胎发生的前几个小时期间核糖体从休眠状态转变为活跃状态的分子证据。休眠核糖体与它们的保守因子相关，形成两个模块，包括Habp4-eEF2和死亡相关蛋白1b（Dap1b）或与eIF5a复合的Dap。这两个模块都占据功能重要的位点，共同作用稳定核糖体和抑制翻译。Dap1b（在哺乳动物中也称为Dapl1）是一种新发现的稳定插入多肽出口通道的翻译抑制剂。加入重组的斑马鱼Dap1b蛋白足以阻断翻译，并在体外哺乳动物翻译提取物中重建休眠的卵细胞核糖体状态。因此，一种发育程序化的保守核糖体状态在核糖体的储存和卵子中的翻译抑制中起着关键作用。

据悉，核糖体在卵发生过程中大量产生，并储存在卵子中。然而，卵子和早期胚胎被翻译抑制。

附：英文原文

Title: A molecular network of conserved factors keeps ribosomes dormant in the egg

Author: Leesch, Friederike, Lorenzo-Orts, Laura, Pribitzer, Carina, Grishkovskaya, Irina, Roehsner, Josef, Chugunova, Anastasia, Matzinger, Manuel, Roitinger, Elisabeth, Belai, Katarina, Kandolf, Susanne, Lin, Tzi-Yang, Mechtler, Karl, Meinhart, Anton, Haselbach, David, Pauli, Andrea

Issue&Volume: 2023-01-18

Abstract: Ribosomes are produced in large quantities during oogenesis and are stored in the egg. However, the egg and early embryo are translationally repressed1,2,3,4. Here, using mass spectrometry and cryo-electron microscopy analyses of ribosomes isolated from zebrafish (Danio rerio) and Xenopus laevis eggs and embryos, we provide molecular evidence that ribosomes transition from a dormant state to an active state during the first hours of embryogenesis. Dormant ribosomes are associated with four conserved factors that form two modules, consisting of Habp4–eEF2 and death associated protein 1b (Dap1b) or Dap in complex with eIF5a. Both modules occupy functionally important sites and act together to stabilize ribosomes and repress translation. Dap1b (also known as Dapl1 in mammals) is a newly discovered translational inhibitor that stably inserts into the polypeptide exit tunnel. Addition of recombinant zebrafish Dap1b protein is sufficient to block translation and reconstitute the dormant egg ribosome state in a mammalian translation extract in vitro. Thus, a developmentally programmed, conserved ribosome state has a key role in ribosome storage and translational repression in the egg.

DOI: 10.1038/s41586-022-05623-y

Source: https://www.nature.com/articles/s41586-022-05623-y

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html