# Inorganic carbon levels regulate growth via SigC signaling cascade in cyanobacteria

## TL;DR

This study reveals how cyanobacteria adjust their growth based on carbon dioxide levels through a specific protein signaling pathway.

## Contribution

The paper identifies a novel signaling cascade involving SigC, Slr1861, and Ssr1600 that regulates cyanobacterial growth in response to inorganic carbon.

## Key findings

- SigC, Slr1861, and Ssr1600 form a signaling cascade that connects cyanobacterial growth to environmental CO2 levels.
- High CO2 causes excessive RNAP-SigC holoenzyme formation, reducing photosynthesis and causing cell lysis in ΔrpoZ cells.
- Reducing Ssr1600 levels in suppressor mutants restores normal growth and gene expression in high CO2 conditions.

## Abstract

Cyanobacterial growth depends on inorganic carbon (Ci; CO2 and bicarbonate) concentration, but mechanism(s) adjusting photosynthesis and growth according to Ci remain unclear. ΔrpoZ cells lacking the ω subunit of the RNA polymerase (RNAP) show a unique high‐CO2 lethal phenotype in Synechocystis sp. PCC 6803.Bioinformatics, biochemical and 3D modeling studies were used to reveal how suppressor mutations rescue ΔrpoZ cells in 3% CO2.Suppressor mutations were mapped to the ssr1600 gene. Ssr1600 was shown to function as an anti‐σ factor antagonist. The Slr1861 protein was identified as an anti‐σ factor and as an Ssr1600 kinase. The Slr1861/Ssr1600 pair was shown to control the formation of RNAP‐SigC holoenzyme using a phosphorylation‐controlled partner‐switching mechanism. In high CO2, excess formation of growth‐limiting RNAP‐SigC holoenzyme in ΔrpoZ reduces the expression of cell wall synthesis, photosynthetic and nutrient uptake genes, leading to low photosynthesis activity and cell lysis. In the suppressor mutants, drastically decreased Ssr1600 levels lowered the amounts of RNAP‐SigC holoenzyme to similar levels as in the control strain, returning an almost normal transcriptome composition, photosynthesis and growth.The results indicate that SigC, Slr1861 and Ssr1600 proteins form a growth‐regulating signaling cascade in cyanobacteria, which connects growth to environmental Ci levels.

Cyanobacterial growth depends on inorganic carbon (Ci; CO2 and bicarbonate) concentration, but mechanism(s) adjusting photosynthesis and growth according to Ci remain unclear. ΔrpoZ cells lacking the ω subunit of the RNA polymerase (RNAP) show a unique high‐CO2 lethal phenotype in Synechocystis sp. PCC 6803.

Bioinformatics, biochemical and 3D modeling studies were used to reveal how suppressor mutations rescue ΔrpoZ cells in 3% CO2.

Suppressor mutations were mapped to the ssr1600 gene. Ssr1600 was shown to function as an anti‐σ factor antagonist. The Slr1861 protein was identified as an anti‐σ factor and as an Ssr1600 kinase. The Slr1861/Ssr1600 pair was shown to control the formation of RNAP‐SigC holoenzyme using a phosphorylation‐controlled partner‐switching mechanism. In high CO2, excess formation of growth‐limiting RNAP‐SigC holoenzyme in ΔrpoZ reduces the expression of cell wall synthesis, photosynthetic and nutrient uptake genes, leading to low photosynthesis activity and cell lysis. In the suppressor mutants, drastically decreased Ssr1600 levels lowered the amounts of RNAP‐SigC holoenzyme to similar levels as in the control strain, returning an almost normal transcriptome composition, photosynthesis and growth.

The results indicate that SigC, Slr1861 and Ssr1600 proteins form a growth‐regulating signaling cascade in cyanobacteria, which connects growth to environmental Ci levels.