Communication and Cross-Regulation between Chemically Fueled Sender and Receiver Reaction Networks

Nature connects multiple fuel-driven chemical/enzymatic reaction networks (CRNs/ERNs) via cross-regulation to hierarchically control biofunctions for a tailored adaption in complex sensory landscapes. Herein, we introduce a facile example of communication and cross-regulation among two fuel-driven DNA-based ERNs regulated by a concatenated RNA transcription regulator. ERN1 (sender) is designed for the fuel-driven promoter formation for T7 RNA polymerase, which activates RNA transcription. The produced RNA can deactivate or activate DNA in ERN2 (receiver) by toehold-mediated strand displacement, leading to a communication between two ERNs. The RNA from ERN1 can repress or promote the fuel-driven state of ERN2; ERN2 in turn feedbacks to regulate the lifetime of ERN1. Furthermore, the incorporation of RNase H allows for RNA degradation and enables the autonomous recovery of ERN2. We believe that concatenation of multiple CRNs/ERNs provides a basis for the design of more elaborate autonomous regulatory mechanisms in systems chemistry and synthetic biology.

Automated summary

Nature achieves hierarchical control of biofunctions in complex sensory landscapes through cross-regulation of multiple fuel-driven chemical/enzymatic reaction networks (CRNs/ERNs). We present a simple example of communication and cross-regulation between two fuel-driven DNA-based ERNs using a concatenated RNA transcription regulator. The RNA produced by ERN1 can activate or deactivate DNA in ERN2, establishing communication between the two ERNs. The incorporation of RNase H enables RNA degradation and autonomous recovery of ERN2. We propose that concatenation of multiple CRNs/ERNs can be used to design more elaborate autonomous regulatory mechanisms in systems chemistry and synthetic biology.