An interaction between eIF4A3 and eIF3g drives the internal initiation of translation.
An interaction between eIF4A3 and eIF3g drives the internal initiation of translation.
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DOI：
10.1093/nar/gkad763
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发表时间：
2023-11-10
影响因子：
14.9
通讯作者：
中科院分区：
文献类型：
--
作者：
RNA结构或修饰的RNA序列可以为核糖体加载和内部翻译起始提供平台。内部翻译的功能重要性最近被发现，一个子集的环状RNA（circRNA）是内部翻译。然而，circRNA内部翻译起始的分子机制仍不清楚。在这里，我们确定eIF 3g（eIF 3复合物的亚基）作为eIF 4A 3的结合伴侣，eIF 4A 3是外显子连接复合物（EJC）的核心成分，沉积在剪接的mRNA上，在基因表达的调控中起着多种作用。eIF 4A 3-eIF 3g之间的直接相互作用充当eIF 4A 3和eIF 3复合物之间的分子接头，从而促进内部核糖体进入。体外合成的circRNA的蛋白质合成证明了eIF 4A 3驱动的内部翻译，其依赖于eIF 4A 3-eIF 3g相互作用。此外，我们的全转录组分析表明，内源性circRNA的有效多核糖体缔合需要eIF 4A 3。值得注意的是，内源性circRNA的子集可以以eIF 4A 3依赖性方式表达全长完整蛋白质，例如β-连环蛋白。总的来说，我们的研究结果扩展了对人类转录组（包括circRNA）蛋白质编码潜力的理解。
An RNA structure or modified RNA sequences can provide a platform for ribosome loading and internal translation initiation. The functional significance of internal translation has recently been highlighted by the discovery that a subset of circular RNAs (circRNAs) is internally translated. However, the molecular mechanisms underlying the internal initiation of translation in circRNAs remain unclear. Here, we identify eIF3g (a subunit of eIF3 complex) as a binding partner of eIF4A3, a core component of the exon-junction complex (EJC) that is deposited onto spliced mRNAs and plays multiple roles in the regulation of gene expression. The direct interaction between eIF4A3-eIF3g serves as a molecular linker between the eIF4A3 and eIF3 complex, thereby facilitating internal ribosomal entry. Protein synthesis from in vitro-synthesized circRNA demonstrates eIF4A3-driven internal translation, which relies on the eIF4A3-eIF3g interaction. Furthermore, our transcriptome-wide analysis shows that efficient polysomal association of endogenous circRNAs requires eIF4A3. Notably, a subset of endogenous circRNAs can express a full-length intact protein, such as β-catenin, in an eIF4A3-dependent manner. Collectively, our results expand the understanding of the protein-coding potential of the human transcriptome, including circRNAs.
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由类似 IRES 的短元件驱动的环状 RNA 的普遍翻译
影响因子：
16.6
作者：
Fan X;Yang Y;Chen C;Wang Z
通讯作者：
Wang Z
影响因子：
14.9
作者：
Park J;Chang J;Hwang HJ;Jeong K;Lee HJ;Ha H;Park Y;Lim C;Woo JS;Kim YK
通讯作者：
Kim YK
影响因子：
16.8
作者：
Gudikote, JP;Imam, JS;Wilkinson, MF
通讯作者：
Wilkinson, MF
影响因子：
46.9
作者：
Fredriksson, S;Gullberg, M;Landegren, U
通讯作者：
Landegren, U
DOI：
10.1073/pnas.1218732110
发表时间：
2013-04-09
影响因子：
11.1
作者：
Chazal, Pierre-Etienne;Daguenet, Elisabeth;Le Hir, Herve
通讯作者：
Le Hir, Herve