Human eIF3: from 'blobology' to biological insight.
Human eIF3: from 'blobology' to biological insight.
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DOI：
10.1098/rstb.2016.0176
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发表时间：
2017-03-19
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影响因子：
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通讯作者：
Cate JH
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作者：
Cate JH
真核生物中的翻译在启动期间受到高度调节，这是一个受到细胞状态的众多读数影响的过程。在许多情况下，细胞信使RNA可能不遵循翻译起始的经典“扫描”机制，但这些途径背后的分子机制仍在探索中。一些RNA病毒如丙型肝炎病毒使用称为内部核糖体进入位点（IRES）的高度结构化的RNA元件，其通过使用与一般真核翻译起始因子eIF 3的特异性相互作用来征用真核翻译起始。在这里，我提出的证据表明，除了其在翻译中的一般作用，eIF 3在人类和可能在所有多细胞真核生物也作为一个翻译激活剂或抑制剂，通过结合特定mRNA的5′-非翻译区的RNA结构，类似于在转录中的介体复合物的作用。此外，多细胞真核生物中的eIF 3还含有一个5′ 7-甲基鸟苷帽结合亚基eIF 3d，它在特定mRNA的翻译中取代了一般的帽结合起始因子eIF 4 E。基于eIF 3的细胞生物学、生物化学和结构研究结果，人类翻译起始可能通过数十种不同的分子途径进行，其中绝大多数仍有待探索。这篇文章是主题问题“核糖体的观点”的一部分。
Translation in eukaryotes is highly regulated during initiation, a process impacted by numerous readouts of a cell's state. There are many cases in which cellular messenger RNAs likely do not follow the canonical ‘scanning’ mechanism of translation initiation, but the molecular mechanisms underlying these pathways are still being uncovered. Some RNA viruses such as the hepatitis C virus use highly structured RNA elements termed internal ribosome entry sites (IRESs) that commandeer eukaryotic translation initiation, by using specific interactions with the general eukaryotic translation initiation factor eIF3. Here, I present evidence that, in addition to its general role in translation, eIF3 in humans and likely in all multicellular eukaryotes also acts as a translational activator or repressor by binding RNA structures in the 5′-untranslated regions of specific mRNAs, analogous to the role of the mediator complex in transcription. Furthermore, eIF3 in multicellular eukaryotes also harbours a 5′ 7-methylguanosine cap-binding subunit—eIF3d—which replaces the general cap-binding initiation factor eIF4E in the translation of select mRNAs. Based on results from cell biological, biochemical and structural studies of eIF3, it is likely that human translation initiation proceeds through dozens of different molecular pathways, the vast majority of which remain to be explored. This article is part of the themed issue ‘Perspectives on the ribosome’.