An La-related protein controls cell cycle arrest by nuclear retrograde transport of tRNAs during diapause formation in Artemia

在卤虫休眠形成过程中,La 相关蛋白通过 tRNA 的核逆向运输来控制细胞周期停滞

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作者:Dian-Fu Chen, Cheng Lin, Hong-Liang Wang, Li Zhang, Li Dai, Sheng-Nan Jia, Rong Zhou, Ran Li, Jin-Shu Yang, Fan Yang, James S Clegg, Hiromichi Nagasawa, Wei-Jun Yang

Background

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.

Conclusions

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.

Results

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. Conclusions: 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.

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