eIF4E-binding protein regulation of mRNAs with differential 5'-UTR secondary structure: a polyelectrostatic model for a component of protein-mRNA interactions.
eIF4E-binding protein regulation of mRNAs with differential 5'-UTR secondary structure: a polyelectrostatic model for a component of protein-mRNA interactions.
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DOI：
10.1093/nar/gks511
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发表时间：
2012-09
影响因子：
14.9
通讯作者：
Warwicker J
中科院分区：
文献类型：
--
作者：
Cawley A;Warwicker J
真核生物中的翻译控制是复杂的，取决于各种因子与mRNA的结合。将酵母eIF 4 E结合蛋白（4 E-BP）缺失突变体中特异性上调和下调的mRNA亚群的可用数据与已报道的mRNA二级结构测量结果相结合，以研究亚群之间的5′-UTR二级结构是否存在差异。caf 20 Δ突变体中翻译效率上调的基因具有相对较高的平均5′-UTR二级结构。RNA结合蛋白的偏好性与5′-UTR二级结构的增加没有明显的广泛相关性，这使我们推测二级结构本身可能在eIF 4 E/4 E-BP抑制和eIF 4 E/eIF 4G翻译起始之间的mRNA差异分配中发挥作用。Caf 20 p和Eap 1 p在预测的无序区域都含有正电荷。这些区域也存在于eIF 4G中，并已报道与mRNA结合相关。这些片段围绕典型eIF 4 E结合基序的模式在每个4 E-BP和eIF 4G之间变化。基因本体的分析表明，酵母蛋白含有预测的无序片段，与正电荷运行，富集核酸结合。我们建议，4 E-BP的行为，在一定程度上，作为差异，灵活，多静电支架的mRNA。
Control of translation in eukaryotes is complex, depending on the binding of various factors to mRNAs. Available data for subsets of mRNAs that are translationally up- and down-regulated in yeast eIF4E-binding protein (4E-BP) deletion mutants are coupled with reported mRNA secondary structure measurements to investigate whether 5′-UTR secondary structure varies between the subsets. Genes with up-regulated translational efficiencies in the caf20Δ mutant have relatively high averaged 5′-UTR secondary structure. There is no apparent wide-scale correlation of RNA-binding protein preferences with the increased 5′-UTR secondary structure, leading us to speculate that the secondary structure itself may play a role in differential partitioning of mRNAs between eIF4E/4E-BP repression and eIF4E/eIF4G translation initiation. Both Caf20p and Eap1p contain stretches of positive charge in regions of predicted disorder. Such regions are also present in eIF4G and have been reported to associate with mRNA binding. The pattern of these segments, around the canonical eIF4E-binding motif, varies between each 4E-BP and eIF4G. Analysis of gene ontology shows that yeast proteins containing predicted disordered segments, with positive charge runs, are enriched for nucleic acid binding. We propose that the 4E-BPs act, in part, as differential, flexible, polyelectrostatic scaffolds for mRNAs.
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