eIF3 and Its mRNA-Entry-Channel Arm Contribute to the Recruitment of mRNAs With Long 5'-Untranslated Regions.
eIF3 and Its mRNA-Entry-Channel Arm Contribute to the Recruitment of mRNAs With Long 5'-Untranslated Regions.
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DOI：
10.3389/fmolb.2021.787664
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发表时间：
2021
影响因子：
5
通讯作者：
Aitken CE
中科院分区：
文献类型：
--
作者：
Stanciu A;Luo J;Funes L;Galbokke Hewage S;Aitken CE
真核生物的翻译起始是一个多步骤的过程，也是翻译过程中最受调控的阶段。真核起始因子3（eIF 3）是翻译起始因子中最大和最复杂的，它参与了整个起始途径中的事件。特别是，eIF 3似乎在mRNA募集中发挥关键作用。最近，eIF 3被认为与驱动特定类型mRNA的选择性翻译有关。然而，解开这些不同的贡献机制，并解开eIF 3复合物的各个亚基的作用仍然具有挑战性。我们采用核糖体分析的芽殖酵母细胞表达两个不同的突变靶向eIF 3复合物。这些突变要么破坏整个复合物，要么破坏位于核糖体mRNA进入通道附近的亚基，这些亚基似乎在mRNA结合和起始密码子识别过程中或响应于mRNA结合和起始密码子识别而重新定位。破坏整个eIF 3复合物或特异性靶向这些亚基会影响具有长5′-非翻译区的mRNA，其翻译更依赖于eIF 4A、eIF 4 B和Ded 1，但较少依赖于eIF 4G、eIF 4 E和PABP。整个eIF 3复合物的破坏进一步影响参与线粒体过程和具有结构化5′-非翻译区的mRNA。对两种突变最敏感的mRNA与对整个复合物破坏唯一敏感的mRNA的比较揭示了eIF 3复合物单个亚基的特定作用。
Translation initiation in eukaryotes is a multi-step pathway and the most regulated phase of translation. Eukaryotic initiation factor 3 (eIF3) is the largest and most complex of the translation initiation factors, and it contributes to events throughout the initiation pathway. In particular, eIF3 appears to play critical roles in mRNA recruitment. More recently, eIF3 has been implicated in driving the selective translation of specific classes of mRNAs. However, unraveling the mechanism of these diverse contributions—and disentangling the roles of the individual subunits of the eIF3 complex—remains challenging. We employed ribosome profiling of budding yeast cells expressing two distinct mutations targeting the eIF3 complex. These mutations either disrupt the entire complex or subunits positioned near the mRNA-entry channel of the ribosome and which appear to relocate during or in response to mRNA binding and start-codon recognition. Disruption of either the entire eIF3 complex or specific targeting of these subunits affects mRNAs with long 5′-untranslated regions and whose translation is more dependent on eIF4A, eIF4B, and Ded1 but less dependent on eIF4G, eIF4E, and PABP. Disruption of the entire eIF3 complex further affects mRNAs involved in mitochondrial processes and with structured 5′-untranslated regions. Comparison of the suite of mRNAs most sensitive to both mutations with those uniquely sensitive to disruption of the entire complex sheds new light on the specific roles of individual subunits of the eIF3 complex.
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影响因子：
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作者：
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影响因子：
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