Browse by author
Lookup NU author(s): Miron Leanca, Dr Yulia YuzenkovaORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2026. Circadian biological clocks evolved across kingdoms of life as an adaptation to predictable cycles of sunrise and sunset. In the cyanobacterium Synechococcuselongatus, a protein-based clock precisely controls when different genes are turned on and off during the 24-h day but the phasing mechanism remains unclear. Here we show the molecular basis of this regulation and reconstitute clock-controlled transcription in vitro using purified components. Biochemical and structural analyses revealed that the clock-regulated transcription factor RpaA can function as either an activator or a repressor of cyanobacterial RNA polymerase, depending on its binding position relative to core promoter elements. Leveraging the repressor mechanism, we developed a heterologous in vitro system driven by bacteriophage T7 RNA polymerase that sustains circadian transcription for multiple days. These findings explain how a single clock output generates opposite phases of gene expression and define the minimal components for circadian clock function, enabling synthetic or biotechnological applications.
Author(s): Fang M, Gu Y, Leanca M, Matyszewski M, LiWang A, Yuzenkova Y, Corbett KD, Golden SS
Publication type: Article
Publication status: Published
Journal: Nature Structural and Molecular Biology
Year: 2026
Volume: 33
Pages: 275-281
Online publication date: 10/02/2026
Acceptance date: 16/12/2025
Date deposited: 25/02/2026
ISSN (print): 1545-9993
ISSN (electronic): 1545-9985
Publisher: Springer Nature
URL: https://doi.org/10.1038/s41594-025-01740-0
DOI: 10.1038/s41594-025-01740-0
Data Access Statement: The cryo-EM reconstructions of the S. elongatus RNAP, RpaA–promoter complex and RpaA TAC were deposited to the EM Data Bank under accession numbers EMD-47221, EMD-47222 and EMD-47223, respectively. Corresponding coordinates were deposited to the PDB under accession numbers 9DVS, 9DVT and 9DVU. All other data are available in the main text or the Extended data files. Source data are provided with this paper. Extended data is available for this paper at https://doi.org/10.1038/s41594-025-01740-0
Altmetrics provided by Altmetric
