小柯机器人

美国斯坦福大学医学院Maria Barna研究小组发现，演化差异的mTOR重塑翻译组来促进组织再生。2023年7月26日，国际知名学术期刊《自然》在线发表了这一成果。

研究人员证明了蛋白质合成的快速激活是蝾螈（Ambystoma mexicanum）肢体再生关键的损伤反应的一个独特特征。通过应用多聚体测序技术，研究人员确定了数百种转录本，包括抗氧化剂和核糖体成分，这些转录本在翻译水平上选择性地激活了原有信使RNA对损伤的反应。相比之下，蛋白质合成在小鼠非再生性趾骨截断时不会被激活。研究人员发现mTORC1通路是介导蝾螈组织再生和翻译控制的关键上游信号。研究人员发现在两栖动物中，mTOR蛋白序列有独特的扩展。

通过在人体细胞中改造蝾螈两栖动物的 mTOR（axmTOR），研究人员发现这些变化产生了一种超敏激酶，使蝾螈两栖动物能够将这一通路维持在高度易变的状态，以便迅速激活。这种变化使蝾螈的mTOR对营养感应更加敏感，而氨基酸转运的抑制足以抑制组织再生。这些发现共同凸显了翻译组对协调高度再生物种伤口愈合早期步骤的意外影响，并为人们了解脊椎动物的再生潜力提供了一个缺失的环节。

据了解，生物学中的一个重要的谜题是，为什么某些物种（如蝾螈）可以再生组织，而哺乳动物却不能。

附：英文原文

Title: Evolutionarily divergent mTOR remodels translatome for tissue regeneration

Author: Zhulyn, Olena, Rosenblatt, Hannah D., Shokat, Leila, Dai, Shizhong, Kuzuoglu-ztrk, Duygu, Zhang, Zijian, Ruggero, Davide, Shokat, Kevan M., Barna, Maria

Issue&Volume: 2023-07-26

Abstract: An outstanding mystery in biology is why some species, such as the axolotl, can regenerate tissues whereas mammals cannot1. Here, we demonstrate that rapid activation of protein synthesis is a unique feature of the injury response critical for limb regeneration in the axolotl (Ambystoma mexicanum). By applying polysome sequencing, we identify hundreds of transcripts, including antioxidants and ribosome components that are selectively activated at the level of translation from pre-existing messenger RNAs in response to injury. By contrast, protein synthesis is not activated in response to non-regenerative digit amputation in the mouse. We identify the mTORC1 pathway as a key upstream signal that mediates tissue regeneration and translational control in the axolotl. We discover unique expansions in mTOR protein sequence among urodele amphibians. By engineering an axolotl mTOR (axmTOR) in human cells, we show that these changes create a hypersensitive kinase that allows axolotls to maintain this pathway in a highly labile state primed for rapid activation. This change renders axolotl mTOR more sensitive to nutrient sensing, and inhibition of amino acid transport is sufficient to inhibit tissue regeneration. Together, these findings highlight the unanticipated impact of the translatome on orchestrating the early steps of wound healing in a highly regenerative species and provide a missing link in our understanding of vertebrate regenerative potential.

DOI: 10.1038/s41586-023-06365-1

Source: https://www.nature.com/articles/s41586-023-06365-1

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