Departments of Genetics and Developmental Biology, Stanford University, Stanford, CA, USA.
Department of Biology, Stanford University, Stanford, CA, USA.
Nat Rev Genet. 2018 Jul;19(7):431-452. doi: 10.1038/s41576-018-0008-z.
Regulation of mRNA translation offers the opportunity to diversify the expression and abundance of proteins made from individual gene products in cells, tissues and organisms. Emerging evidence has highlighted variation in the composition and activity of several large, highly conserved translation complexes as a means to differentially control gene expression. Heterogeneity and specialized functions of individual components of the ribosome and of the translation initiation factor complexes eIF3 and eIF4F, which are required for recruitment of the ribosome to the mRNA 5' untranslated region, have been identified. In this Review, we summarize the evidence for selective mRNA translation by components of these macromolecular complexes as a means to dynamically control the translation of the proteome in time and space. We further discuss the implications of this form of gene expression regulation for a growing number of human genetic disorders associated with mutations in the translation machinery.
mRNA 翻译的调控为细胞、组织和生物体中从单个基因产物产生的蛋白质的表达和丰度的多样化提供了机会。新出现的证据强调了几个大型、高度保守的翻译复合物的组成和活性的变化，这是一种差异化控制基因表达的手段。核糖体和翻译起始因子复合物 eIF3 和 eIF4F 的单个成分的异质性和专门功能，这些成分对于核糖体招募到 mRNA 5'非翻译区是必需的，已经被确定。在这篇综述中，我们总结了这些大分子复合物的成分通过选择性的 mRNA 翻译来动态控制蛋白质组在时间和空间上翻译的证据。我们还进一步讨论了这种基因表达调控形式对越来越多与翻译机制突变相关的人类遗传疾病的影响。
