TOB Proteins Repress Translation via the CCR4–NOT Deadenylase Complex Independent of Deadenylation

IF 1.3 4区 生物学 Q4 CELL BIOLOGY
Genes to Cells Pub Date : 2025-08-04 DOI:10.1111/gtc.70042
Kanae Miyazaki, Takumi Tomohiro, Yoshinori Funakami, Akira Fukao, Toru Suzuki, Tadashi Yamamoto, Toshinobu Fujiwara
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引用次数: 0

Abstract

Transducer of ErbB2 (TOB) proteins have been shown to promote mRNA decay through interactions with the CCR4–NOT complex and poly(A)-binding protein (PABP). While their role in deadenylation-mediated mRNA degradation is well established, their potential function in translational control remains to be elucidated. Here, we employed an in vitro translation system combined with an RNA tethering strategy to examine the function of TOB1 and TOB2 in translation. Our results demonstrate that TOB1 and TOB2 act as repressors of translation initiation, independent of deadenylation. Notably, this translational repression selectively targets eIF4A-dependent translation, while translation driven by eIF4A-independent IRES elements remains unaffected. While the interaction between TOB proteins and PABP appears to be dispensable, as disruption of this interaction only partially reduces translational repression, the knockdown of CNOT1, the scaffold of the CCR4–NOT complex, substantially relieves this repression, highlighting its indispensable role in the mechanism. Collectively, our findings uncover a previously unrecognized function of TOB proteins as direct repressors of translation initiation, independent of mRNA decay, and highlight a specific reliance on eIF4A activity and CCR4–NOT complex integrity.

Abstract Image

TOB蛋白通过独立于去烯化的CCR4-NOT去烯化酶复合物抑制翻译
ErbB2 (TOB)蛋白的换能器通过与CCR4-NOT复合物和聚(A)结合蛋白(PABP)的相互作用促进mRNA的衰变。虽然它们在去烯基化介导的mRNA降解中的作用已经得到了很好的证实,但它们在翻译控制中的潜在功能仍有待阐明。本研究采用体外翻译系统结合RNA系固策略来检测TOB1和TOB2在翻译中的功能。我们的研究结果表明,TOB1和TOB2作为翻译起始的抑制因子,独立于死基化。值得注意的是,这种翻译抑制选择性地靶向依赖eif4a的翻译,而不依赖eif4a的IRES元件驱动的翻译不受影响。虽然TOB蛋白和PABP之间的相互作用似乎是必不可少的,因为这种相互作用的破坏只能部分地减少翻译抑制,但CCR4-NOT复合物的支架CNOT1的敲低可以大大减轻这种抑制,突出了其在该机制中不可或缺的作用。总的来说,我们的研究结果揭示了TOB蛋白作为翻译起始的直接抑制因子的先前未被认识到的功能,独立于mRNA衰变,并强调了对eIF4A活性和CCR4-NOT复合物完整性的特定依赖。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Genes to Cells
Genes to Cells 生物-细胞生物学
CiteScore
3.40
自引率
0.00%
发文量
71
审稿时长
3 months
期刊介绍: Genes to Cells provides an international forum for the publication of papers describing important aspects of molecular and cellular biology. The journal aims to present papers that provide conceptual advance in the relevant field. Particular emphasis will be placed on work aimed at understanding the basic mechanisms underlying biological events.
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