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Modulation of Eukaryotic mRNA Stability via the Cap-binding Translation Complex eIF4F.

机译:通过帽结合翻译复合物eIF4F的真核mRNA稳定性的调节。

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Decapping by Dcp1 in Saccharomyces cerevisiae is a key step in mRNA degradation. However, the cap also binds the eukaryotic initiation factor (eIF) complex 4F and its associated proteins. Characterisation of the relationship between decapping and interactions involving eIF4F is an essential step towards understanding polysome disassembly and mRNA decay. Three types of observation suggest how changes in the functional status of eIF4F modulate mRNA stability in vivo. First, partial disruption of the interaction between eIF4E and eIF4G, caused by mutations in eIF4E or the presence of the yeast 4E-binding protein p20, stabilised mRNAs. The interactions of eIF4G and p20 with eIF4E may therefore act to modulate the decapping process. Since we also show that the in vitro decapping rate is not directly affected by the nature of the body of the mRNA, this suggests that changes in eIF4F structure could play a role in triggering decapping during mRNA decay. Second, these effects were seen in the absence of extreme changes in global translation rates in the cell, and are therefore relevant to normal mRNA turnover. Third, a truncated form of eIF4E (Delta196) had a reduced capacity to inhibit Dcp1-mediated decapping in vitro, yet did not change cellular mRNA half-lives. Thus, the accessibility of the cap to Dcp1 in vivo is not simply controlled by competition with eIF4E, but is subject to switching between molecular states with different levels of access. (c) 2002 Elsevier Science Ltd.
机译:酿酒酵母中的Dcp1脱盖是mRNA降解中的关键步骤。然而,该帽还结合了真核起始因子(eIF)复合物4F及其相关蛋白。脱盖和涉及eIF4F的相互作用之间的关系的表征是理解多核糖体分解和mRNA衰减的重要步骤。三种观察类型表明eIF4F功能状态的变化如何调节体内mRNA的稳定性。首先,由于eIF4E中的突变或酵母4E结合蛋白p20的存在而引起的eIF4E和eIF4G之间相互作用的部分破坏,稳定了mRNA。因此,eIF4G和p20与eIF4E的相互作用可能起到调节脱盖过程的作用。由于我们还显示了体外的去盖化率不受mRNA本体性质的直接影响,因此表明eIF4F结构的改变可能在mRNA衰减期间触发去盖化作用。第二,在细胞中整体翻译率没有极端变化的情况下可以看到这些作用,因此与正常的mRNA转换有关。第三,截短形式的eIF4E(Delta196)在体外抑制Dcp1介导的脱盖的能力降低,但并未改变细胞mRNA的半衰期。因此,帽在体内对Dcp1的可及性不仅可以通过与eIF4E的竞争来简单控制,而且还可以在具有不同可及性水平的分子状态之间进行切换。 (c)2002爱思唯尔科学有限公司。

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