Gray N K, Wickens M
Department of Biochemistry, University of Wisconsin, Madison 53706, USA.
Annu Rev Cell Dev Biol. 1998;14:399-458. doi: 10.1146/annurev.cellbio.14.1.399.
Regulation of translation initiation is a central control point in animal cells. We review our current understanding of the mechanisms of regulation, drawing particularly on examples in which the biological consequences of the regulation are clear. Specific mRNAs can be controlled via sequences in their 5' and 3' untranslated regions (UTRs) and by alterations in the translation machinery. The 5'UTR sequence can determine which initiation pathway is used to bring the ribosome to the initiation codon, how efficiently initiation occurs, and which initiation site is selected. 5'UTR-mediated control can also be accomplished via sequence-specific mRNA-binding proteins. Sequences in the 3' untranslated region and the poly(A) tail can have dramatic effects on initiation frequency, with particularly profound effects in oogenesis and early development. The mechanism by which 3'UTRs and poly(A) regulate initiation may involve contacts between proteins bound to these regions and the basal translation apparatus. mRNA localization signals in the 3'UTR can also dramatically influence translational activation and repression. Modulations of the initiation machinery, including phosphorylation of initiation factors and their regulated association with other proteins, can regulate both specific mRNAs and overall translation rates and thereby affect cell growth and phenotype.
翻译起始的调控是动物细胞中的一个核心控制点。我们回顾了目前对调控机制的理解，特别借鉴了调控的生物学后果清晰的例子。特定的信使核糖核酸（mRNA）可通过其5'和3'非翻译区（UTR）中的序列以及翻译机制的改变来进行控制。5'UTR序列可以决定使用哪种起始途径将核糖体带到起始密码子，起始发生的效率如何，以及选择哪个起始位点。5'UTR介导的控制也可以通过序列特异性的mRNA结合蛋白来实现。3'非翻译区和聚腺苷酸（poly(A)）尾中的序列可以对起始频率产生显著影响，在卵子发生和早期发育中影响尤为深远。3'UTR和poly(A)调节起始的机制可能涉及与这些区域结合的蛋白质和基础翻译装置之间的相互作用。3'UTR中的mRNA定位信号也可以显著影响翻译激活和抑制。起始机制的调节，包括起始因子的磷酸化及其与其他蛋白质的调控性结合，可以调节特定的mRNA和整体翻译速率，从而影响细胞生长和表型。
