MOLECULAR CLOCKWORK OF BACTERIAL TIME-KEEPING [O'SHEA LAB]
March 28th, 2013
The day-night cycle is the most predictable environmental variation on Earth. Many organisms, ranging from bacteria to humans have evolved endogenous time-keeping mechanisms, called circadian clocks that are used to anticipate and respond to this environmental cycle. Circadian clocks, despite being genetically unrelated, share a set of fundamental properties such as free-running (keeping a 24-hr period in a constant environment), entrainment (matching their periods to the environmental cycle) and temperature compensation (keeping the period relatively insensitive to temperature). In one of the simplest model systems known to possess such a time-keeping mechanism – the cyanobacterium Synechococcus elongatus - the core clock consists of a three-protein oscillator KaiA, KaiB and KaiC that interact to generate circadian oscillations of KaiC phosphorylation that in turn are essential for producing the oscillatory patterns of gene expression. The molecular mechanisms through which the KaiABC clock relays the timing information to circadian gene expression remain less understood.
In this paper, published in Molecular Cell (AOP), we addressed how the KaiABC clock controls the activation of a key circadian transcription factor, RpaA. We find that two histidine kinases, CikA and SasA, interpret different states of the Kai clock and act as transducers of temporal information by converging on RpaA. SasA and CikA are activated by the KaiABC clock at different times of the day and regulate RpaA in opposite ways – one increases its activity by phosphorylating it and the other one decreases it, through dephosphorylation. This sequential action of two opposing enzyme produces an oscillation of RpaA activity that is offset from that of the KaiABC core clock. Such a mechanism of generating offset oscillations are potentially used in other circadian systems and could also be important for a better time-telling in the face of cellular and environmental fluctuations.