bims-ciryme 2024-08-25 papers

Proc Natl Acad Sci U S A. 2024 Aug 27. 121(35): e2408322121

A circadian clock output functions independently of phyB to sustain daytime PIF3 degradation.

Wei Liu, Harper Lowrey, Anxu Xu, Chun Chung Leung, Christopher Adamchek, Jiangman He, Juan Du, Meng Chen, Joshua M Gendron.

The circadian clock is an endogenous oscillator, and its importance lies in its ability to impart rhythmicity on downstream biological processes, or outputs. Our knowledge of output regulation, however, is often limited to an understanding of transcriptional connections between the clock and outputs. For instance, the clock is linked to plant growth through the gating of photoreceptors via rhythmic transcription of the nodal growth regulators, PHYTOCHROME-INTERACTING FACTORs (PIFs), but the clock's role in PIF protein stability is less clear. Here, we identified a clock-regulated, F-box type E3 ubiquitin ligase, CLOCK-REGULATED F-BOX WITH A LONG HYPOCOTYL 1 (CFH1), that specifically interacts with and degrades PIF3 during the daytime. Additionally, genetic evidence indicates that CFH1 functions primarily in monochromatic red light, yet CFH1 confers PIF3 degradation independent of the prominent red-light photoreceptor phytochrome B (phyB). This work reveals a clock-mediated growth regulation mechanism in which circadian expression of CFH1 promotes sustained, daytime PIF3 degradation in parallel with phyB signaling.

Keywords: PIF3; circadian clock; photomorphogenesis; post-translational modification; red light signaling

DOI: https://doi.org/10.1073/pnas.2408322121

Proc Natl Acad Sci U S A. 2024 Aug 27. 121(35): e2402697121

Circadian and environmental signal integration in a natural population of Arabidopsis.

Haruki Nishio, Dora L Cano-Ramirez, Tomoaki Muranaka, Luíza Lane de Barros Dantas, Mie N Honjo, Jiro Sugisaka, Hiroshi Kudoh, Antony N Dodd.

Plants sense and respond to environmental cues during 24 h fluctuations in their environment. This requires the integration of internal cues such as circadian timing with environmental cues such as light and temperature to elicit cellular responses through signal transduction. However, the integration and transduction of circadian and environmental signals by plants growing in natural environments remains poorly understood. To gain insights into 24 h dynamics of environmental signaling in nature, we performed a field study of signal transduction from the nucleus to chloroplasts in a natural population of Arabidopsis halleri. Using several modeling approaches to interpret the data, we identified that the circadian clock and temperature are key regulators of this pathway under natural conditions. We identified potential time-delay steps between pathway components, and diel fluctuations in the response of the pathway to temperature cues that are reminiscent of the process of circadian gating. We found that our modeling framework can be extended to other signaling pathways that undergo diel oscillations and respond to environmental cues. This approach of combining studies of gene expression in the field with modeling allowed us to identify the dynamic integration and transduction of environmental cues, in plant cells, under naturally fluctuating diel cycles.

Keywords: circadian rhythms; field biology; signal transduction; state-space modeling

DOI: https://doi.org/10.1073/pnas.2402697121

Nat Commun. 2024 Aug 22. 15(1): 7205

Time-of-day effects of cancer drugs revealed by high-throughput deep phenotyping.

Carolin Ector, Christoph Schmal, Jeff Didier, Sébastien De Landtsheer, Anna-Marie Finger, Francesca Müller-Marquardt, Johannes H Schulte, Thomas Sauter, Ulrich Keilholz, Hanspeter Herzel, Achim Kramer, Adrián E Granada.

The circadian clock, a fundamental biological regulator, governs essential cellular processes in health and disease. Circadian-based therapeutic strategies are increasingly gaining recognition as promising avenues. Aligning drug administration with the circadian rhythm can enhance treatment efficacy and minimize side effects. Yet, uncovering the optimal treatment timings remains challenging, limiting their widespread adoption. In this work, we introduce a high-throughput approach integrating live-imaging and data analysis techniques to deep-phenotype cancer cell models, evaluating their circadian rhythms, growth, and drug responses. We devise a streamlined process for profiling drug sensitivities across different times of the day, identifying optimal treatment windows and responsive cell types and drug combinations. Finally, we implement multiple computational tools to uncover cellular and genetic factors shaping time-of-day drug sensitivity. Our versatile approach is adaptable to various biological models, facilitating its broad application and relevance. Ultimately, this research leverages circadian rhythms to optimize anti-cancer drug treatments, promising improved outcomes and transformative treatment strategies.

DOI: https://doi.org/10.1038/s41467-024-51611-3

Cell Rep. 2024 Aug 20. pii: S2211-1247(24)01014-3. [Epub ahead of print]43(9): 114663

Non-canonical metabolic and molecular effects of calorie restriction are revealed by varying temporal conditions.

Heidi H Pak, Allison N Grossberg, Rachel R Sanderfoot, Reji Babygirija, Cara L Green, Mikaela Koller, Monika Dzieciatkowska, Daniel A Paredes, Dudley W Lamming.

Calorie restriction (CR) extends lifespan and healthspan in diverse species. Comparing ad libitum- and CR-fed mice is challenging due to their significantly different feeding patterns, with CR-fed mice consuming their daily meal in 2 h and then subjecting themselves to a prolonged daily fast. Here, we examine how ad libitum- and CR-fed mice respond to tests performed at various times and fasting durations and find that the effects of CR-insulin sensitivity, circulating metabolite levels, and mechanistic target of rapamycin 1 (mTORC1) activity-result from the specific temporal conditions chosen, with CR-induced improvements in insulin sensitivity observed only after a prolonged fast, and the observed differences in mTORC1 activity between ad libitum- and CR-fed mice dependent upon both fasting duration and the specific tissue examined. Our results demonstrate that much of our understanding of the effects of CR are related to when, relative to feeding, we choose to examine the mice.

Keywords: CP: Metabolism; aging; calorie restriction; dietary restriction; fasting; lifespan; mTOR; time-restricted feeding

DOI: https://doi.org/10.1016/j.celrep.2024.114663