Cell State Transitions Drive Transcriptome-Proteome Alignment in a Minimal Photoautotroph
- 1Baylor University
Abstract
The cyanobacterium Prochlorococcus marinus MED4 is a minimal photoautotroph that maintains circadian regulation despite its reduced circadian regulatory toolkit relative to other cyanobacteria. Moreover, MED4, like other small prokaryotes, has low transcript counts per cell and poor transcriptome-proteome alignment. A systems-level understanding of how MED4 uses its minimal regulatory machinery to achieve a well-coordinated circadian cycle is currently lacking. We address this knowledge gap by analyzing global proteomics, transcriptomics, metabolomics, and lipidomics collected across a circadian day. Integrating these data with statistical analyses, enzyme-constrained metabolic modeling, and stochastic mathematical modeling allows us to reveal and characterize six major population-level cell states. Here we present evidence that high-light response regulator RpaB plays an important night-time regulatory role in MED4 by inhibiting RpaA, the master transcriptional activator of dusk genes and HimA, a regulatory target of RpaA previously shown to influence DNA conformation, is highly correlated with global transcriptome-proteome alignment (R2 = 0.67, p < 0.001). We construct stochastic differential equations consistent with genome-wide promotion of transcription by HimA as a plausible mechanism. Our HimA-driven model recapitulates alignment dynamics (R2 = 0.59, p < 0.01) as one plausible explanation. Collectively, our results elucidate how a minimal circadian regulatory program achieves robust coordination across transcriptional, translational, and metabolic levels
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BibTeX
@misc{rozum2026cell,
title = {{Cell State Transitions Drive Transcriptome-Proteome Alignment in a Minimal Photoautotroph}},
author = {J. C. Rozum and X. Li and Y.-M. Kim and Z. D. Johnson and W. Sineath and M. Garcia and N. Sadler and P. Bohutskyi and M. Cheung and W.-J. QIAN and S. Feng},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.20.760503},
url = {https://www.biorxiv.org/content/10.64898/2026.10.20.760503v1},
note = {CC0},
}
RIS
TY - UNPB
TI - Cell State Transitions Drive Transcriptome-Proteome Alignment in a Minimal Photoautotroph
AU - J. C. Rozum
AU - X. Li
AU - Y.-M. Kim
AU - Z. D. Johnson
AU - W. Sineath
AU - M. Garcia
AU - N. Sadler
AU - P. Bohutskyi
AU - M. Cheung
AU - W.-J. QIAN
AU - S. Feng
PY - 2026
DA - 2026/10/20
PB - bioRxiv
DO - 10.64898/2026.10.20.760503
UR - https://www.biorxiv.org/content/10.64898/2026.10.20.760503v1
AB - The cyanobacterium Prochlorococcus marinus MED4 is a minimal photoautotroph that maintains circadian regulation despite its reduced circadian regulatory toolkit relative to other cyanobacteria. Moreover, MED4, like other small prokaryotes, has low transcript counts per cell and poor transcriptome-proteome alignment. A systems-level understanding of how MED4 uses its minimal regulatory machinery to achieve a well-coordinated circadian cycle is currently lacking. We address this knowledge gap by analyzing global proteomics, transcriptomics, metabolomics, and lipidomics collected across a circadian day. Integrating these data with statistical analyses, enzyme-constrained metabolic modeling, and stochastic mathematical modeling allows us to reveal and characterize six major population-level cell states. Here we present evidence that high-light response regulator RpaB plays an important night-time regulatory role in MED4 by inhibiting RpaA, the master transcriptional activator of dusk genes and HimA, a regulatory target of RpaA previously shown to influence DNA conformation, is highly correlated with global transcriptome-proteome alignment (R2 = 0.67, p < 0.001). We construct stochastic differential equations consistent with genome-wide promotion of transcription by HimA as a plausible mechanism. Our HimA-driven model recapitulates alignment dynamics (R2 = 0.59, p < 0.01) as one plausible explanation. Collectively, our results elucidate how a minimal circadian regulatory program achieves robust coordination across transcriptional, translational, and metabolic levels
ER -