Cap-independent translation is required for starvation-induced differentiation in yeast
Cap-independent translation is required for starvation-induced differentiation in yeast
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DOI：
10.1126/science.1144467
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发表时间：
2007-08-31
期刊：
影响因子：
56.9
通讯作者：
Doudna, Jennifer A.
中科院分区：
文献类型：
--
作者：
Gilbert, Wendy V.;Zhou, Kaihong;Doudna, Jennifer A.
细胞内部核糖体进入位点（IRES）是mRNA转录物的非翻译片段，其被认为响应于阻止典型5 '帽依赖性翻译的环境应激而启动蛋白质合成。尽管许多细胞mRNA被认为具有IRES，但没有一个具有已证实的生理功能或分子机制。在这里，我们表明，七个酵母基因所需的侵入性生长，营养限制诱导的发育途径，含有有效的IRES，需要启动因子eIF4G帽独立翻译。与病毒IRES基于RNA结构的活性相反，我们发现非结构化的富含A的元件通过将poly（A）结合蛋白（Pab 1）募集到侵入性生长信息的5 '非翻译区（UTR）来介导内部起始。削弱IRES活性的5 'UTR突变会损害侵入性生长，这表明对应激的生理适应需要不依赖于帽的翻译。
Cellular internal ribosome entry sites ( IRESs) are untranslated segments of mRNA transcripts thought to initiate protein synthesis in response to environmental stresses that prevent canonical 5' cap-dependent translation. Although numerous cellular mRNAs are proposed to have IRESs, none has a demonstrated physiological function or molecular mechanism. Here we show that seven yeast genes required for invasive growth, a developmental pathway induced by nutrient limitation, contain potent IRESs that require the initiation factor eIF4G for cap-independent translation. In contrast to the RNA structure-based activity of viral IRESs, we show that an unstructured A-rich element mediates internal initiation via recruitment of the poly( A) binding protein ( Pab1) to the 5' untranslated region ( UTR) of invasive growth messages. A 5' UTR mutation that impairs IRES activity compromises invasive growth, which indicates that cap-independent translation is required for physiological adaptation to stress.