Guo Jinhu, Cheng Ping, Yuan Haiyan, Liu Yi
Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Cell. 2009 Sep 18;138(6):1236-46. doi: 10.1016/j.cell.2009.06.043. Epub 2009 Sep 10.
The eukaryotic circadian oscillators consist of autoregulatory negative feedback loops. However, little is known about the role of posttranscriptional regulation of RNA in circadian oscillators. In the Neurospora circadian negative feedback loop, FRQ and FRH form the FFC complex that represses frq transcription. Here, we show that FFC also binds frq RNA and interacts with the exosome to regulate frq RNA decay. Consequently, frq RNA is robustly rhythmic as it is more stable when FRQ levels are low. Silencing of RRP44, the catalytic subunit of the exosome, elevates frq RNA levels and impairs clock function. In addition, rrp44 is a clock-controlled gene and a direct target of the WHITE COLLAR complex, and RRP44 controls the circadian expression of some ccgs. Taken together, these results suggest that FFC and the exosome are part of a posttranscriptional negative feedback loop that regulates frq transcript levels and the circadian output pathway.
真核生物的昼夜节律振荡器由自动调节的负反馈回路组成。然而，关于RNA的转录后调控在昼夜节律振荡器中的作用，人们知之甚少。在粗糙脉孢菌的昼夜节律负反馈回路中，FRQ和FRH形成FFC复合物，该复合物抑制frq转录。在此，我们表明FFC也结合frq RNA并与外切体相互作用以调节frq RNA的降解。因此，frq RNA具有很强的节律性，因为当FRQ水平较低时它更稳定。外切体的催化亚基RRP44的沉默会提高frq RNA水平并损害时钟功能。此外，rrp44是一个受时钟调控的基因，是白领复合物的直接靶标，并且RRP44控制一些ccg的昼夜节律表达。综上所述，这些结果表明FFC和外切体是转录后负反馈回路的一部分，该回路调节frq转录本水平和昼夜节律输出途径。
