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Structure of the RNA Specialized Translation Initiation Element that Recruits eIF3 to the 5'-UTR of c-Jun.
Journal of Molecular Biology ( IF 4.7 ) Pub Date : 2020-01-14 , DOI: 10.1016/j.jmb.2020.01.001
Matthew J Walker 1 , Matthew D Shortridge 1 , Dreycey D Albin 1 , Lauren Y Cominsky 1 , Gabriele Varani 1
Affiliation  

Specialized translation initiation is a novel form of regulation of protein synthesis, whereby RNA structures within the 5'-UTR regulate translation rates of specific mRNAs. Similar to internal ribosome entry sites (IRESs), specialized translation initiation requires the recruitment of eukaryotic initiation factor 3 (eIF3), but also requires cap recognition by eIF3d, a new 5'-m7GTP recognizing protein. How these RNA structures mediate eIF3 recruitment to affect translation of specific mRNAs remains unclear. Here, we report the nuclear magnetic resonance (NMR) structure of a stem-loop within the c-JUN 5' UTR recognized by eIF3 and essential for specialized translation initiation of this well-known oncogene. The structure exhibits similarity to eIF3 recognizing motifs found in hepatitis C virus (HCV)-like IRESs, suggesting mechanistic similarities. This work establishes the RNA structural features involved in c-JUN specialized translation initiation and provides a basis to search for small molecule inhibitors of aberrant expression of the proto-oncogenic c-JUN.

中文翻译:


将 eIF3 招募到 c-Jun 的 5'-UTR 的 RNA 专门翻译起始元件的结构。



专门的翻译起始是蛋白质合成调节的一种新形式,通过 5'-UTR 内的 RNA 结构调节特定 mRNA 的翻译速率。与内部核糖体进入位点 (IRES) 类似,专门的翻译起始需要招募真核起始因子 3 (eIF3),但也需要 eIF3d(一种新的 5'-m7GTP 识别蛋白)进行帽识别。这些 RNA 结构如何介导 eIF3 募集以影响特定 mRNA 的翻译仍不清楚。在这里,我们报告了 eIF3 识别的 c-JUN 5' UTR 内茎环的核磁共振 (NMR) 结构,该结构对于这一众所周知的癌基因的专门翻译起始至关重要。该结构与丙型肝炎病毒 (HCV) 样 IRES 中发现的 eIF3 识别基序相似,表明机制相似。这项工作建立了参与 c-JUN 专门翻译起始的 RNA 结构特征,并为寻找原癌 c-JUN 异常表达的小分子抑制剂提供了基础。
更新日期:2020-01-14
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