Cate Jamie H D
Departments of Chemistry and Molecular and Cell Biology, University of California, Berkeley, CA 94720-3220, USA
Lawrence Berkeley National Laboratory, Division of Molecular Biophysics and Integrated Bioimaging, Berkeley, CA 94720, USA.
Philos Trans R Soc Lond B Biol Sci. 2017 Mar 19;372(1716). doi: 10.1098/rstb.2016.0176.
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'.
在真核生物中，翻译起始过程受到高度调控，该过程受细胞状态的众多读数影响。在许多情况下，细胞信使核糖核酸（mRNA）可能并不遵循典型的翻译起始“扫描”机制，但其背后的分子机制仍有待揭示。一些RNA病毒，如丙型肝炎病毒，利用高度结构化的RNA元件，即内部核糖体进入位点（IRES），通过与一般真核翻译起始因子eIF3的特定相互作用来操控真核翻译起始。在此，我提供证据表明，除了在翻译中的一般作用外，人类以及可能所有多细胞真核生物中的eIF3还通过结合特定mRNA 5'非翻译区的RNA结构，充当翻译激活剂或抑制剂，类似于中介复合物在转录中的作用。此外，多细胞真核生物中的eIF3还含有一个5' 7-甲基鸟苷帽结合亚基——eIF3d，它在某些mRNA的翻译中取代了一般的帽结合起始因子eIF4E。基于对eIF3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。本文是主题为“核糖体的视角”特刊的一部分。
