Regulation of the Neurospora circadian clock by an RNA helicase
Regulation of the Neurospora circadian clock by an RNA helicase
复制标题
DOI：
10.1101/gad.1266805
复制
发表时间：
2005-01-15
影响因子：
10.5
通讯作者：
Liu, Y
中科院分区：
文献类型：
--
作者：
Cheng, P;He, Q;Liu, Y
真核生物的昼夜节律振荡器由自我调节的负反馈环组成。FRQ、WC-1和WC-2是脉孢霉昼夜节律振荡器负反馈回路的三个已知成分。FRQ通过与WC-1/WC-2复合体相互作用抑制自身转录，抑制WC在转录激活中的作用。在这里，我们发现所有的FRQ都与FRH有关，FRH是脉孢子菌中一种重要的含有死盒的RNA解旋酶。FRH的芽生酵母同源物Dobip/Mtr4p是真核生物中RNA代谢的重要调节因子--外体的辅因子。通过诱导发夹RNA的表达下调FRH导致低水平的FRQ而高水平的FRQ RNA和昼夜节律的取消。FRH与WC复合体相关，这种相互作用在FRQ零应变中保持。通过删除FRQ中的一个结构域来破坏FRQ-FRH复合体，消除了FRQ-WC之间的相互作用，表明FRH介导了FRQ和WC复合体之间的相互作用。这些数据表明，FRH是昼夜节律负反馈环中的重要组成部分，并揭示了RNA解旋酶在调控基因转录中出人意料的作用。
The eukaryotic circadian oscillators consist of autoregulatory negative-feedback loops. FRQ, WC-1, and WC-2 are three known components of the negative-feedback loop of the Neurospora circadian oscillator. FRQ represses its own transcription by interacting with the WC-1/WC-2 complex and inhibiting WC's role in transcriptional activation. Here we show that all FRQ associates with FRH, an essential DEAD box-containing RNA helicase in Neurospora. The budding yeast homolog of FRH, Dobip/Mtr4p, is a cofactor of exosome, an important regulator of RNA metabolism in eukaryotes. Down-regulation of FRH by inducible expression of a hairpin RNA leads to low levels of FRQ but high levels of frq RNA and the abolishment of circadian rhythmicities. FRH is associated with the WC complex and this interaction is maintained in a frq null strain. Disruption of the FRQ-FRH complex by deleting a domain in FRQ eliminates the FRQ-WC interaction, suggesting that FRH mediates the interaction between FRQ and the WC complex. These data demonstrate that FRH is an essential component in the circadian negative-feedback loop and reveal an unexpected role of an RNA helicase in regulating gene transcription.