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Nature:eIF3的一个特定功能

摘要 : “真核细胞启动因子-3”(eIF3)过去被认为是一个普遍性的翻译启动因子,然而其失控却会导致组织特异性效应。

 “真核细胞启动因子-3”(eIF3)过去被认为是一个普遍性的翻译启动因子,然而其失控却会导致组织特异性效应。在这项研究中,Jamie Cate及同事通过PAR-CLIP全转录组分析显示,eIF3只是一个子类的信使RNA(主要涉及细胞增殖、分化和凋亡)的翻译所必需的,并且能产生翻译激发或翻译抑制作用。eIF3的失调已被与一些癌症联系起来,关于eIF3控制一类专门化的基因的表达的发现表明,抑制eIF3与特定mRNA的结合可能是一个有希望的抗癌策略。

原文链接:

eIF3 targets cell-proliferation messenger RNAs for translational activation or repression

原文摘要:Regulation of protein synthesis is fundamental for all aspects of eukaryotic biology by controlling development, homeostasis and stress responses. The 13-subunit, 800-kilodalton eukaryotic initiation factor 3 (eIF3) organizes initiation factor and ribosome interactions required for productive translation. However, current understanding of eIF3 function does not explain genetic evidence correlating eIF3 deregulation with tissue-specific cancers and developmental defects. Here we report the genome-wide discovery of human transcripts that interact with eIF3 using photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP). eIF3 binds to a highly specific program of messenger RNAs involved in cell growth control processes, including cell cycling, differentiation and apoptosis, via the mRNA 5′ untranslated region. Surprisingly, functional analysis of the interaction between eIF3 and two mRNAs encoding the cell proliferation regulators c-JUN and BTG1 reveals that eIF3 uses different modes of RNA stem–loop binding to exert either translational activation or repression. Our findings illuminate a new role for eIF3 in governing a specialized repertoire of gene expression and suggest that binding of eIF3 to specific mRNAs could be targeted to control carcinogenesis.

来源: Nature 浏览次数:0

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