RNA is an attractive biomolecule for biosensing and engineering applications due to its information storage capacity and ability to drive gene expression or knockdown. However, methods to link chemical signals to the production of specific RNAs are lacking. Here, we develop protease-responsive RNA polymerases (PRs) as a strategy to encode multiple specific proteolytic events in defined sequences of RNA in live mammalian cells. This work demonstrates that RNAP-based molecular recording devices can be deployed for multimodal analyses of biochemical activities or to trigger gene circuits using measured signaling events.

ID 53021 Poster Board 323Physiological responses to catecholamines in many organs, such as the heart, airways, and pancreas, rely on accurate signaling through the beta 2 adrenergic receptor (B2AR), a prototypical G protein-coupled receptor. It is becoming increasingly clear that a complete B2AR physiological response is integrated from many discrete receptor signaling events, separated in time, that originate from different subcellular locations in cells. The spatiotemporal fidelity of these discrete signaling events relies on two critical processes-those that localize receptors to specific compartments, and those that ensure that the receptors couple to the correct signaling components in these compartments. The biochemical networks that mediate these processes, however, are still not fully understood.