Circadian rhythm is an autoregulatory rhythm, which is sustained by various mechanisms. The nucleocytoplasmic shuttling of BMAL1 is essential for CLOCK translocation between cytoplasm and nucleus and maintenance of the correct pace of the circadian clock. Here we showed that RAE1 and NUP98 can promote the degradation of BMAL1 and CLOCK. Knockdown of RAE1 and NUP98 suppressed BMAL1 shuttling, leading to cytoplasm accumulation of CLOCK. Furthermore, Chip assay showed that knockdown of RAE1 and NUP98 can enhance the interaction between CLOCK: BMAL1 and E-box region in the promoters of Per2 and Cry1 while reducing its transcription activation activity. Our present study firstly revealed that RAE1 and NUP98 are critical regulators for BMAL1 shuttling.

昼夜节律是一种自我调节节律，由多种机制维持。 BMAL1 的核质穿梭对于细胞质和细胞核之间的 CLOCK 易位以及维持生物钟的正确节奏至关重要。在这里我们表明RAE1和NUP98可以促进BMAL1和CLOCK的降解。 RAE1 和 NUP98 的敲低抑制了 BMAL1 穿梭，导致 CLOCK 细胞质积累。此外，芯片分析表明，敲低RAE1和NUP98可以增强CLOCK：BMAL1与Per2和Cry1启动子中E-box区域之间的相互作用，同时降低其转录激活活性。我们目前的研究首先揭示了 RAE1 和 NUP98 是 BMAL1 穿梭的关键调节因子。