ZFP36L1 is an RNA-binding protein responsible for mRNA decay in the cytoplasm. ZFP36L1 has also been suggested as a nuclear-cytoplasmic shuttling protein because it contains a potential nuclear localization signal and a nuclear export signal. However, it remains unclear how the nuclear localization of ZFP36L1 is controlled. In this study, we provide evidence that the nuclear accumulation of ZFP36L1 protein is modulated in a cell cycle-dependent manner. ZFP36L1 protein accumulation in fractionated nuclei was particularly prominent in G1/S-phase-arrested cells, while it was downregulated in S-phase cells, and eventually disappeared in G2-phase nuclei. Moreover, forced nuclear targeting of ZFP36L1 revealed marked downregulation in S-/G2-phase cells, suggesting that ZFP36L1 can be eliminated in the nucleus. The C-terminal serine-rich cluster of ZFP36L1 is critical for the regulation of its nuclear accumulation because truncation of this probable disordered region enhanced the nuclear localization of ZFP36L1, increased its stability, and abolished its cell cycle-dependent fluctuations. These findings provide the first hints to the question of how ZFP36L1 nuclear accumulation is controlled during the course of the cell cycle.

中文翻译：

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ZFP36L1的核积累是细胞周期依赖性的，并由富含C端丝氨酸的簇决定。

ZFP36L1是负责细胞质中mRNA降解的RNA结合蛋白。ZFP36L1还被建议作为核质穿梭蛋白，因为它包含潜在的核定位信号和核输出信号。但是，尚不清楚如何控制ZFP36L1的核定位。在这项研究中，我们提供的证据表明ZFP36L1蛋白的核积累以细胞周期依赖性方式被调节。在G1 / S期停滞的细胞中，ZFP36L1蛋白在分级细胞核中的积累尤为突出，而在S期细胞中则被下调，并最终在G2期细胞核中消失。此外，ZFP36L1的强制核靶向显示S- / G2期细胞中明显下调，这表明ZFP36L1可在细胞核中消除。ZFP36L1的富含C端丝氨酸的簇对于调节其核积累至关重要，因为该可能无序区的截短增强了ZFP36L1的核定位，增加了其稳定性，并消除了其依赖于细胞周期的波动。这些发现首次提示了在细胞周期过程中如何控制ZFP36L1核积累的问题。