Translational regulation of Hsp90 mRNA -: AUG-proximal 5′-untranslated region elements essential for preferential heat shock translation
Translational regulation of Hsp90 mRNA -: AUG-proximal 5′-untranslated region elements essential for preferential heat shock translation
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DOI：
10.1074/jbc.m404681200
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发表时间：
2004-11-26
影响因子：
4.8
通讯作者：
Duncan, RF
中科院分区：
文献类型：
--
作者：
Ahmed, R;Duncan, RF
果蝇的热休克导致大多数正常（非热休克）mRNA翻译的抑制和热休克mRNA的优先翻译。在果蝇中，Hsp22和Hsp70 mrna的优先翻译序列元件定位于5'-非翻译区（5'-UTR）。在热休克mRNA中，Hsp90 mRNA的独特之处在于其5'-UTR具有广泛的二级结构，并且在非热休克细胞中大量存在。在本研究中，我们发现Hsp90 mRNA的翻译在正常生长温度下是低效的，并且在热休克下被大量激活。它的优先翻译不是基于ires介导的翻译途径，因为过表达eIF4E-BP会抑制其翻译（以及Hsp70 mRNA的翻译）。Hsp90 mRNA的优先翻译能力是由其5'-UTR决定的，但与Hsp22和-70不同的是，它主要受AUG起始密码子附近核苷酸的影响。我们提出了一个模型来解释Hsp90 mRNA翻译，结果表明热休克抑制eIF4F活性，Hsp90 mRNA翻译对eIF4F失活敏感。
Heat shock in Drosophila results in repression of most normal (non-heat shock) mRNA translation and the preferential translation of the heat shock mRNAs. The sequence elements that confer preferential translation have been localized to the 5'-untranslated region (5'-UTR) for Hsp22 and Hsp70 mRNAs (in Drosophila). Hsp90 mRNA is unique among the heat shock mRNAs in having extensive secondary structure in its 5'-UTR and being abundantly represented in the non-heat shocked cell. In this study, we show that Hsp90 mRNA translation is inefficient at normal growth temperature, and substantially activated by heat shock. Its preferential translation is not based on an IRES-mediated translation pathway, because overexpression of eIF4E-BP inhibits its translation (and the translation of Hsp70 mRNA). The ability of Hsp90 mRNA to be preferentially translated is conferred by its 5'-UTR, but, in contrast to Hsp22 and -70, is primarily influenced by nucleotides close to the AUG initiation codon. We present a model to account for Hsp90 mRNA translation, incorporating results indicating that heat shock inhibits eIF4F activity, and that Hsp90 mRNA translation is sensitive to eIF4F inactivation.