德克萨斯大学西南医学中心研究人员在最新一期的Cell杂志上发表生物昼夜节律分子机理研究成果文章The Exosome Regulates Circadian Gene Expression in a Posttranscriptional Negative Feedback Loop。
真核生物通的昼夜节律调节器包含自动调整负调节反馈回路。然而，科学家们对转录后的RNA对昼夜调节的作用却知之甚少。
德克萨斯大学西南医学中心刘一教授研究组以脉孢菌为模型，发现负反馈回路，FRQ和来自FFC复合物的FRH共同抑制frq的转录。研究发现FFC结合在frq RNA是上，与外核体相互协调共同调控frq RNA的衰退。结果，当FRQ低水平时，frq RNA粗略的控制生物昼夜节律。如果frq RNA水平降低，RRP44被沉默会导致昼夜节律功能受损。
此外，研究发现rrp44是个节律控制基因，它的基因表达产物直接作用于WHITE COLLAR复合物，RRP44通过表达ccgs来控制节律。这些实验表明，FFC和外核体是组成转录后负调控反馈环路的组成部分。（生物谷Bioon.com）
生物谷推荐原始出处：
Cell, Volume 138, Issue 6, 1236-1246, 10 September 2009 doi:10.1016/j.cell.2009.06.043
The Exosome Regulates Circadian Gene Expression in a Posttranscriptional Negative Feedback Loop
Jinhu Guo1, Ping Cheng1, 2, Haiyan Yuan1 and Yi Liu1, ,
1 Department of Physiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
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.
