RT Journal Article
SR Electronic
T1 Dynamic signal processing by ribozyme-mediated RNA circuits to control gene expression
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 016915
DO 10.1101/016915
A1 Shensi Shen
A1 Guillermo Rodrigo
A1 Satya Prakash
A1 Eszter Majer
A1 Thomas E. Landrain
A1 Boris Kirov
A1 José-Antonio Daròs
A1 Alfonso Jaramillo
YR 2015
UL http://biorxiv.org/content/early/2015/03/23/016915.abstract
AB Organisms have different circuitries that allow converting signal molecule levels to changes in gene expression. An important challenge in synthetic biology involves the de novo design of RNA modules enabling dynamic signal processing in live cells. This requires a scalable methodology for sensing, transmission, and actuation, which could be assembled into larger signaling networks. Here, we present a biochemical strategy to design RNA-mediated signal transduction cascades able to sense small molecules and small RNAs. We design switchable functional RNA domains by using strand-displacement techniques. We experimentally characterize the molecular mechanism underlying our synthetic RNA signaling cascades, show the ability to regulate gene expression with transduced RNA signals, and describe the signal processing response of our systems to periodic forcing in single live cells. The engineered systems integrate RNA-RNA interaction with available ribozyme and aptamer elements, providing new ways to engineer arbitrary complex gene circuits.