bims-ciryme 2026-03-22 papers

Proc Natl Acad Sci U S A. 2026 Mar 24. 123(12): e2526714123

Intrinsic period stability of the cyanobacterial circadian oscillator across in vitro and in vivo conditions.

Kumiko Ito-Miwa, Keiko Imai, Kazuki Terauchi, Takao Kondo.

A defining feature of circadian clocks that enables adaptation to Earth's rotation is their ability to sustain an approximately 24 h period with precision, regardless of environmental factors such as temperature. This remarkable reliability of circadian timing can be reconstituted in vitro using only three cyanobacterial clock proteins: KaiA, KaiB, and KaiC. In vivo circadian rhythms, however, are governed not only by this Kai protein-based oscillator but also by transcription-translation feedback loops and additional clock components. The contribution of the Kai protein-based circadian oscillator to the overall reliability of the in vivo circadian rhythm remains unclear. In this study, we compared over 20 KaiC period mutants with periods ranging from 15 to 60 h under in vitro and in vivo conditions. In both cases, the period was insensitive to environmental conditions, suggesting a compensatory mechanism independent of metabolic state or rhythm amplitude. The ATPase activity of KaiC, the pacemaker of the cyanobacterial circadian clock, exhibited a stronger correlation with in vitro circadian frequency than in vivo circadian frequency. These results indicate that the KaiC ATPase-driven protein-based circadian oscillator inherently encodes a reliable circadian period independent of rhythm amplitude or environmental conditions. This intrinsic property likely plays a critical role in preserving the precision and stability of circadian timing in vivo while being influenced by the intracellular environment.

Keywords: KaiC; circadian clock; cyanobacteria; period

DOI: https://doi.org/10.1073/pnas.2526714123

PLoS One. 2026 ;21(3): e0344769

Emergence of appetite and circadian rhythmicity in Atlantic salmon brain transcriptome from endogenous to exogenous feeding.

Sissel Norland, Mariann Eilertsen, Ana S Gomes, David W P Dolan, Rita Karlsen, Ivar Rønnestad, Jon Vidar Helvik.

Successful transition from endogenous yolk utilization to exogenous feeding is critical for survival in fish larvae, yet the changes in the brain during this transition remain incompletely described. In this study, whole-brain RNA sequencing was used to investigate transcriptomic changes over 48 h during endogenous yolk utilization (720 day degrees (dd)) and after the onset of exogenous feeding (920 dd) in Atlantic salmon (Salmo salar), focusing on appetite-related genes. Key components of appetite control, including melanocortin system and nutrient-sensing pathway, were present at 720 dd and elevated levels were observed at 920 dd. Before onset of first feeding, 16 appetite-related genes displayed a significant cyclic profile, where most had a periodicity of 20 h or 28 h. Following the transition from endogenous to exogenous feeding, the majority of significantly cyclic appetite-related genes exhibited a periodicity of 24 h, suggesting the establishment of circadian regulation associated with energy homeostasis. These results indicate that a pre-programmed expression of appetite and energy-related genes occurs in the brain before the yolk is fully utilized. Two weeks into the first feeding period (920 dd), the whole-brain transcriptome showed better responsiveness to feeding, but a fully developed satiety system remained underdeveloped. Additionally, characterization of hypothalamic melanocortin neuropeptides distribution during early salmon development revealed a spatial organization distinct from that reported in later life stages.

DOI: https://doi.org/10.1371/journal.pone.0344769

JCI Insight. 2026 Mar 17. pii: e193622. [Epub ahead of print]

Reciprocal regulation between autism risk gene POGZ and circadian clock.

Ting Wu, Jiao He, Chu-Jun Xu, Chi-Yu Li, Pingchuan Zhang, Yanfeng Wang, Shanshan Zhu, Lusi Zhang, Jingtan Zhu, Jing Zhang, Jia-Da Li, Huadie Liu.

Sleep disturbance is a prevalent yet poorly understood comorbidity in autism spectrum disorders (ASD). Here, we uncover a bidirectional regulatory axis connecting the ASD risk gene POGZ to core circadian mechanisms. We demonstrate that Pogz is widely expressed in the suprachiasmatic nucleus (SCN), the central pacemaker of the circadian rhythms and exhibits circadian oscillations in both the hypothalamus and liver with its transcription directly regulated by the circadian molecule DBP through a D-box element in its proximal enhancer. Pogz-deficient mice exhibited prolonged circadian periodicity, impaired light-induced phase shift, delayed adaption to an 8-hour advance jet-lag, and reduced SCN c-Fos activation in response to light pulses. Mechanistically, POGZ interacts with and enhances the transcription activity of CREB, a key regulator of light-induced phase resetting. Notably, Pogz deletion leads to ASD-related deficits in social novelty and cognition, with cognitive impairments influenced by both photoperiod and behavioral paradigm. Our findings thus reveal a critical, previously unrecognized intersection between an ASD risk gene and circadian clock, offering new insights into the pathogenesis of core ASD symptoms and comorbid sleep disturbances.

Keywords: Behavior; Development; Genetics; Neurodevelopment; Neuroscience

DOI: https://doi.org/10.1172/jci.insight.193622

Nat Plants. 2026 Mar 19.

Stress drives plasticity in leaf ageing transcriptional dynamics in Arabidopsis thaliana.

Joseph Swift, Xuelin Wu, Jiaying Xu, Carl Procko, Tanvi Jain, Natanella Illouz-Eliaz, Joseph R Nery, Joanne Chory, Joseph R Ecker.

Leaf development is dynamic, enabling plants to modulate their growth in response to environmental cues. Under drought conditions, for instance, the model plant Arabidopsis thaliana restricts leaf growth to conserve water, a strategy that enhances water-use efficiency. While this 'stress avoidance' response is well described physiologically, the underlying transcriptional changes that drive such developmental plasticity remain poorly understood. We investigated the transcriptional basis of how drought stress reshapes Arabidopsis leaf development. We profiled 1,226 leaves at various developmental stages and levels of drought stress, and generated a single-nucleus transcriptome atlas comprising ~1 million individual nuclei. We found that drought stress advances transcriptional programmes associated with leaf ageing in a dose-dependent manner, particularly within the mesophyll. These transcriptional shifts scale with stress intensity and correlate with reduced shoot growth, indicating that mesophyll-specific transcriptional changes underlie drought-induced restriction in leaf growth. Overexpression of FERRIC REDUCTION OXIDASE 6 (FRO6) in the mesophyll was sufficient to partially restore leaf growth under drought conditions. Our findings demonstrate how gene expression is reshaped by environmental cues to ensure that shoot architecture is adaptive to stress severity.

DOI: https://doi.org/10.1038/s41477-026-02254-3

Commun Biol. 2026 Mar 21.

β-arrestin1 orchestrates endosomal signaling to regulate translational control of circadian light entrainment.

Brittany Mascarenhas, Shavanie Seecharran, Nicholas A Boehler, Muhammad Wahid, Hai-Ying Mary Cheng.

In mammals, circadian entrainment relies on signaling pathways that translate light input into molecular changes within the central pacemaker, the suprachiasmatic nucleus (SCN). Here, using β‑arrestin1 (ARRB1)-deficient mice, we identify a critical role for β‑arrestin1 in this process, showing that endosomal signaling underlies key steps in clock resetting. We demonstrate that ARRB1 is required for PAC1 receptor internalization and for the activation of endosomal signaling in response to light or PACAP. ARRB1‑dependent PAC1 endosomal signaling activates an ERK1/2-RSK1-S6 cascade that enhances protein translation and contributes to the induction of PER proteins. Transcriptional responses remain intact, underscoring the spatial specificity of ARRB1 function. Our findings position endosomes as critical subcellular hubs for circadian signal transduction and reveal a non-canonical, β-arrestin1-dependent entrainment mechanism that operates through translational control. Together, these results challenge traditional GPCR signaling paradigms and establish endosome-based signaling as a key regulator of circadian timekeeping.

DOI: https://doi.org/10.1038/s42003-026-09905-3