Circadian Control of Global Gene Expression by the Cyanobacterial Master Regulator RpaA

Abstract

The cyanobacterial circadian clock generates genome-wide transcriptional oscillations and regulates cell division, but the underlying mechanisms are not well understood. Here, we show that the response regulator RpaA serves as the master regulator of these clock outputs. Deletion of rpaA abrogates gene expression rhythms globally and arrests cells in a dawn-like expression state. Although rpaA deletion causes core oscillator failure by perturbing clock gene expression, rescuing oscillator function does not restore global expression rhythms. We show that phosphorylated RpaA regulates the expression of not only clock components, generating feedback on the core oscillator, but also a small set of circadian effectors that, in turn, orchestrate genome-wide transcriptional rhythms. Expression of constitutively active RpaA is sufficient to switch cells from a dawn-like to a dusk-like expression state as well as to block cell division. Hence, complex global circadian phenotypes can be generated by controlling the phosphorylation of a single transcription factor.

Role of Type 2 NAD(P)H Dehydrogenase NdbC in Redox Regulation of Carbon Allocation in Synechocystis

“…In addition, the RpaA protein, the master regulator of circadian control, was down-regulated in DndbC in LC (Table III). Its involvement in adjusting the expression levels of enzymes participating in glycolysis and OPP has been shown in Synechococcus elongatus PCC 7942 (Markson et al, 2013). Concerning metabolic reactions downstream from glycolysis, our proteomic analyses did not detect coordinated changes concerning enzymes in the tricarboxylic acid cycle.…”

Redox crisis underlies conditional light–dark lethality in cyanobacterial mutants that lack the circadian regulator, RpaA

“…Additionally, RpaA is important in controlling redox balance, which in turn is very important for regulating metabolism at night. circadian oscillator, which represses the activity of RpaA in the late night/early morning, and subsequently relieves repression throughout the day such that RpaA reaches its peak activity at dusk (19,20,23). This temporal activity pattern, and the fact that RpaA directly binds and activates nighttime metabolism genes (20,24), suggests that it also plays an important role in metabolic control at night.…”

“…circadian oscillator, which represses the activity of RpaA in the late night/early morning, and subsequently relieves repression throughout the day such that RpaA reaches its peak activity at dusk (19,20,23). This temporal activity pattern, and the fact that RpaA directly binds and activates nighttime metabolism genes (20,24), suggests that it also plays an important role in metabolic control at night. Although the transcriptional targets of RpaA have been identified, and it is clear that LD conditions are deleterious to rpaA-null mutants (25), the metabolic and physiological changes that attenuate growth under LD conditions have not been explored.…”

“…The oscillator relays timing information to the SasA-RpaA two-component output pathway, in which RpaA is a transcription factor that binds 170 known downstream gene targets (20,21). RpaA was first identified in another cyanobacterium, Synechocystis sp.…”

“…We recently showed that the circadian clock regulates carbon metabolism in Synechococcus elongatus PCC 7942 as cells transition from the dark into the light during diurnal growth (19). Specifically, in the morning the clock represses the activity of the conserved circadian transcriptional regulator regulator of phycobilisome association A (RpaA), which normally activates nighttime metabolic processes (19,20). This action suppresses primary metabolic processes in the morning, allowing carbon to flow toward secondary metabolic processes when light energy is not limiting (19).…”