An La-related protein controls cell cycle arrest by nuclear retrograde transport of tRNAs during diapause formation in Artemia.
An La-related protein controls cell cycle arrest by nuclear retrograde transport of tRNAs during diapause formation in Artemia.
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La 相关蛋白在卤虫滞育形成过程中通过 tRNA 的核逆行转运控制细胞周期停滞
DOI：
10.1186/s12915-016-0239-4
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发表时间：
2016-03-03
期刊：
影响因子：
5.4
通讯作者：
Yang WJ
中科院分区：
文献类型：
--
作者：
Chen DF;Lin C;Wang HL;Zhang L;Dai L;Jia SN;Zhou R;Li R;Yang JS;Yang F;Clegg JS;Nagasawa H;Yang WJ
在真核生物中，tRNA在细胞核和细胞质之间的运输是一个与细胞周期调控相关的复杂过程。因此，这种运输在细胞生物学中具有根本的重要性，并且该过程的中断对细胞活力和存活具有严重后果。为了科普恶劣的环境，卤虫进化出一种特殊的生殖方式，释放包囊胚胎，细胞分裂可以长期保持在休眠状态。利用卤虫作为一种独特的细胞周期模型，发现卤虫中的一种La相关蛋白Ar-Larp与tRNA结合并在细胞核中积累，导致卤虫细胞周期停滞并控制滞育形成的开始。此外，Ar-Larp的外源基因表达可以诱导癌细胞的细胞周期阻滞，并抑制异种移植小鼠模型中的肿瘤生长，类似于在卤虫滞育胚胎中获得的结果。我们对tRNA运输的研究表明，Ar-Larp通过与tRNA结合并影响其从细胞质到细胞核的逆行运动来控制细胞周期阻滞，这与细胞周期检查点所涉及的途径有关。卤虫中的这些发现为细胞周期阻滞调节的机制提供了新的见解，并提供了一种潜在的新方法来研究tRNA从细胞质到细胞核的逆行运动。
In eukaryotes, tRNA trafficking between the nucleus and cytoplasm is a complex process connected with cell cycle regulation. Such trafficking is therefore of fundamental importance in cell biology, and disruption of this process has grave consequences for cell viability and survival. To cope with harsh habitats, Artemia has evolved a special reproductive mode to release encysted embryos in which cell division can be maintained in a dormancy state for a long period. Using Artemia as a peculiar model of the cell cycle, an La-related protein from Artemia, named Ar-Larp, was found to bind to tRNA and accumulate in the nucleus, leading to cell cycle arrest and controlling the onset of diapause formation in Artemia. Furthermore, exogenous gene expression of Ar-Larp could induce cell cycle arrest in cancer cells and suppress tumor growth in a xenograft mouse model, similar to the results obtained in diapause embryos of Artemia. Our study of tRNA trafficking indicated that Ar-Larp controls cell cycle arrest by binding to tRNAs and influencing their retrograde movement from the cytoplasm to the nucleus, which is connected to pathways involved in cell cycle checkpoints. These findings in Artemia offer new insights into the mechanism underlying cell cycle arrest regulation, as well as providing a potentially novel approach to study tRNA retrograde movement from the cytoplasm to the nucleus.