德克薩斯大學(xué)西南醫(yī)學(xué)中心研究人員在最新一期的Cell雜志上發(fā)表生物晝夜節(jié)律分子機(jī)理研究成果文章The Exosome Regulates Circadian Gene Expression in a Posttranscriptional Negative Feedback Loop。
真核生物通的晝夜節(jié)律調(diào)節(jié)器包含自動(dòng)調(diào)整負(fù)調(diào)節(jié)反饋回路,。然而,,科學(xué)家們對(duì)轉(zhuǎn)錄后的RNA對(duì)晝夜調(diào)節(jié)的作用卻知之甚少。
德克薩斯大學(xué)西南醫(yī)學(xué)中心劉一教授研究組以脈孢菌為模型,,發(fā)現(xiàn)負(fù)反饋回路,,F(xiàn)RQ和來自FFC復(fù)合物的FRH共同抑制frq的轉(zhuǎn)錄。研究發(fā)現(xiàn)FFC結(jié)合在frq RNA是上,,與外核體相互協(xié)調(diào)共同調(diào)控frq RNA的衰退,。結(jié)果,當(dāng)FRQ低水平時(shí),,frq RNA粗略的控制生物晝夜節(jié)律,。如果frq RNA水平降低,RRP44被沉默會(huì)導(dǎo)致晝夜節(jié)律功能受損,。
此外,,研究發(fā)現(xiàn)rrp44是個(gè)節(jié)律控制基因,它的基因表達(dá)產(chǎn)物直接作用于WHITE COLLAR復(fù)合物,RRP44通過表達(dá)ccgs來控制節(jié)律,。這些實(shí)驗(yàn)表明,,F(xiàn)FC和外核體是組成轉(zhuǎn)錄后負(fù)調(diào)控反饋環(huán)路的組成部分。(生物谷Bioon.com)
生物谷推薦原始出處:
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.