eIF3 targets cell-proliferation messenger RNAs for translational activation or repression.
eIF3 targets cell-proliferation messenger RNAs for translational activation or repression.
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DOI：
10.1038/nature14267
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发表时间：
2015-06-04
期刊：
影响因子：
64.8
通讯作者：
Cate JH
中科院分区：
文献类型：
--
作者：
Lee AS;Kranzusch PJ;Cate JH
蛋白质合成的调节是真核生物学的基础，通过控制发育、稳态和应激反应。13亚基，800 kDa的真核起始因子3（eIF 3）组织的起始因子和核糖体相互作用所需的生产性翻译。然而，目前对eIF 3功能的理解并不能解释eIF 3失调与组织特异性癌症和发育缺陷相关的遗传证据。在这里，我们报告了全基因组范围内发现的人类转录本与eIF 3使用光活化交联和免疫沉淀（PAR-CLIP）。eIF 3通过mRNA 5′非翻译区（5′ UTR）与参与细胞生长控制过程（包括细胞周期、分化和凋亡）的信使RNA（mRNA）的高度特异性程序结合。令人惊讶的是，eIF 3和两个mRNA编码细胞增殖调节因子，c-Jun和BTG 1之间的相互作用的功能分析，揭示了eIF 3采用不同的模式的RNA茎环结合发挥翻译激活或抑制。我们的研究结果阐明了eIF 3在管理一个专门的基因表达库中的新作用，并表明eIF 3与特定mRNA的结合可以靶向控制癌变。
Regulation of protein synthesis is fundamental for all aspects of eukaryotic biology by controlling development, homeostasis, and stress responses. The 13-subunit, 800-kDa 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 photo-activatable crosslinking and immunoprecipitation (PAR-CLIP). eIF3 binds to a highly specific programme of messenger RNAs (mRNAs) involved in cell growth control processes, including cell cycling, differentiation, and apoptosis, via the mRNA 5′ untranslated region (5′ UTR). Surprisingly, functional analysis of the interaction between eIF3 and two mRNAs encoding cell proliferation regulators, c-Jun and BTG1, reveals that eIF3 employs 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.