Circadian Rhythms and the Transcriptional Feedback Loop (Nobel Lecture)**

Author(s):  
Michael Rosbash
2015 ◽  
pp. gkv1015 ◽  
Author(s):  
Vladimir Yu. Kiselev ◽  
Veronique Juvin ◽  
Mouhannad Malek ◽  
Nicholas Luscombe ◽  
Phillip Hawkins ◽  
...  

2013 ◽  
Vol 647 ◽  
pp. 391-395
Author(s):  
Liu Sen ◽  
Song Liu

Regulation of daily physiological functions with approximate a 24-hour periodicity, or circadian rhythms, is a characteristic of eukaryotes. So far, cyanobacteria are only known prokaryotes reported to possess circadian rhythmicity. The circadian system in cyanobacteria comprises both a post-translational oscillator (PTO) and a transcriptional/translational feedback loop (TTFL). The PTO can be reconstituted in vitro with three purified proteins (KaiA, KaiB, and KaiC) with the existence of ATP. Phase of the nanoclockwork has been associated with the phosphorylation states of KaiC, with KaiA promoting the phosphorylation of KaiC, and KaiB de-phosphorylating KaiC. Here we studied the evolution of the KaiB protein. The result will be helpful in understanding the evolution of the circadian clock system.


2019 ◽  
Vol 116 (12) ◽  
pp. 5721-5726 ◽  
Author(s):  
Brigitte Grima ◽  
Christian Papin ◽  
Béatrice Martin ◽  
Elisabeth Chélot ◽  
Prishila Ponien ◽  
...  

TheDrosophilacircadian oscillator relies on a negative transcriptional feedback loop, in which the PERIOD (PER) and TIMELESS (TIM) proteins repress the expression of their own gene by inhibiting the activity of the CLOCK (CLK) and CYCLE (CYC) transcription factors. A series of posttranslational modifications contribute to the oscillations of the PER and TIM proteins but few posttranscriptional mechanisms have been described that affect mRNA stability. Here we report that down-regulation of the POP2 deadenylase, a key component of the CCR4–NOT deadenylation complex, alters behavioral rhythms. Down-regulating POP2 specifically increases TIM protein andtimmRNA but nottimpre-mRNA, supporting a posttranscriptional role. Indeed, reduced POP2 levels induce a lengthening oftimmRNA poly(A) tail. Surprisingly, such effects are lost inper0mutants, supporting a PER-dependent inhibition oftimmRNA deadenylation by POP2. We report a deadenylation mechanism that controls the oscillations of a core clock gene transcript.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Guruswamy Mahesh ◽  
Gustavo B. S. Rivas ◽  
Courtney Caster ◽  
Evan B. Ost ◽  
Ravi Amunugama ◽  
...  

Abstract Circadian clocks keep time via ~ 24 h transcriptional feedback loops. In Drosophila, CLOCK-CYCLE (CLK-CYC) activators and PERIOD-TIMELESS (PER-TIM) repressors are feedback loop components whose transcriptional status varies over a circadian cycle. Although changes in the state of activators and repressors has been characterized, how their status is translated to transcriptional activity is not understood. We used mass spectrometry to identify proteins that interact with GFP-tagged CLK (GFP-CLK) in fly heads at different times of day. Many expected and novel interacting proteins were detected, of which several interacted rhythmically and were potential regulators of protein levels, activity or transcriptional output. Genes encoding these proteins were tested to determine if they altered circadian behavior via RNAi knockdown in clock cells. The NIPPED-A protein, a scaffold for the SAGA and Tip60 histone modifying complexes, interacts with GFP-CLK as transcription is activated, and reducing Nipped-A expression lengthens circadian period. RNAi analysis of other SAGA complex components shows that the SAGA histone deubiquitination (DUB) module lengthened period similarly to Nipped-A RNAi knockdown and weakened rhythmicity, whereas reducing Tip60 HAT expression drastically weakened rhythmicity. These results suggest that CLK-CYC binds NIPPED-A early in the day to promote transcription through SAGA DUB and Tip60 HAT activity.


Endocrinology ◽  
2012 ◽  
Vol 153 (1) ◽  
pp. 1-5 ◽  
Author(s):  
Paolo Sassone-Corsi

Abstract A wide variety of endocrine, physiological, and metabolic functions follow daily oscillations. Most of these regulations are controlled at the level of gene expression by the circadian clock and, a remarkably coordinated transcription-translation machinery that exerts its function in virtually all mammalian cells. A large fraction of the genome is under control of the circadian clock, a regulation that is achieved through dynamic changes in chromatin states. Recent findings have demonstrated intimate connections between the circadian clock and epigenetic control. The case of nicotinamide adenine dinucleotide, which modulates the circadian activity of the deacetylase sirtuin 1, constitutes a paradigmatic example of the link between cyclic cellular metabolism and chromatin remodeling. Indeed, the clock transcriptional feedback loop is interlocked with the enzymatic loop of the nicotinamide adenine dinucleotide salvage pathway.


2012 ◽  
Vol 32 (22) ◽  
pp. 4585-4594 ◽  
Author(s):  
E. Kowalska ◽  
J. A. Ripperger ◽  
C. Muheim ◽  
B. Maier ◽  
Y. Kurihara ◽  
...  

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