Cho - Graphical Abstract

来自韩国首尔大学基础科学研究所的V. Narry Kim实验室发现在胚胎干细胞中LIN28A是一种涉及到ER蛋白翻译的抑制子,这篇文章刊登在最新一期《CELL》杂志上。

-2012年11月9日《细胞》


中文翻译


【题目】在胚胎干细胞中LIN28A是一种涉及到ER蛋白翻译的抑制子

【译文】在发育的转变、葡萄糖代谢和肿瘤发生过程中,LIN28具有重要的作用。在分子水平,LIN28被认为可以抑制 let-7 microRNAs的成熟并提高某一mRNAs的转录。在这项研究中,我们利用RNA交联-免疫沉淀作用-测序(CLIP-seq)和核糖体足迹技术获得了小鼠胚胎干细胞中LIN28A分子功能的全基因组图谱。我们发现除了let-7前体外,LIN28A结合在大量的被剪接的mRNAs上。LIN28A识别AAGNNG,AAGNG和频率较少的UGUG,这些序列位于小发卡结构环的末段。LIN28A被聚集于内质网(ER)上并抑制mRNA的翻译(这些mRNA是以ER为目的地的),这样可以减少跨膜蛋白、ER或高尔基蛋白和分泌蛋白的合成。我们的研究结果证明了一种选择性的涉及ER翻译的调节机制,并且证明了在分泌途径中LIN28A作为基因的全局抑制子的作用。

英文原稿


[Title]LIN28AIs a Suppressor of ER-Associated Translation in Embryonic Stem Cells

[Authors]Jun Cho, Hyeshik Chang, S. Chul Kwon, Baekgyu Kim, Yoosik Kim, Junho Choe, Minju Ha, Yoon Ki Kim, V. Narry Kim

[Abstract]LIN28 plays a critical role in developmental transition, glucose metabolism, and tumorigenesis. At the molecular level, LIN28 is known to repress maturation of let-7 microRNAs and enhance translation of certain mRNAs. In this study, we obtain a genome-wide view of the molecular function of LIN28Ain mouse embryonic stem cells by carrying out RNA crosslinking-immunoprecipitation-sequencing (CLIP-seq) and ribosome footprinting. We find that, in addition to let-7 precursors, LIN28Abinds to a large number of spliced mRNAs. LIN28Arecognizes AAGNNG, AAGNG, and less frequently UGUG, which are located in the terminal loop of a small hairpin. LIN28Ais localized to the periendoplasmic reticulum (ER) area and inhibits translation of mRNAs that are destined for the ER, reducing the synthesis of transmembrane proteins, ER or Golgi lumen proteins, and secretory proteins. Our study suggests a selective regulatory mechanism for ER-associated translation and reveals an unexpected role of LIN28Aas a global suppressor of genes in the secretory pathway.

原文地址

http://www.cell.com/abstract/S0092-8674(12)01234-2

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