Abstract
BackgroundIn 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.ResultsUsing 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.ConclusionsThese 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12915-016-0239-4) contains supplementary material, which is available to authorized users.
Highlights
In eukaryotes, tRNA trafficking between the nucleus and cytoplasm is a complex process connected with cell cycle regulation
Our results indicated that tRNA trafficking regulates the mitogenesis and proliferation of cells through cell cycle checkpoints, a process that is mediated by multiple signaling pathways including histone H3 acetylated at lysine 56 (H3K56ac), extracellular signal-regulated kinase (ERK), and Akt
To determine the cell division state in each developmental stage, Western blotting was performed to analyze the expression of the mitosis markers CDK6, cyclin D3, phosphorylated Rb at Thr356, and phosphorylated histone H3 at Ser10, all of which were strongly inhibited in the diapause and post-diapause stages (Fig. 1b)
Summary
TRNA trafficking between the nucleus and cytoplasm is a complex process connected with cell cycle regulation Such trafficking is of fundamental importance in cell biology, and disruption of this process has grave consequences for cell viability and survival. TRNA trafficking between the nucleus and the cytoplasm is a complex process that often responds to environmental stress, thereby connecting transcription in the nucleus to translation in the cytoplasm [6]. This trafficking is of fundamental importance to cell biology, and disruption of this process has grave consequences for cell viability and survival. The function of Tef1/2 is required for efficient tRNA nuclear export [14] and is dependent on Msn and Mtr, as is the tRNA retrograde transport pathway [15]
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