RNA synthetic biology inspired from bacteria: construction of transcription attenuators under antisense regulation.
Among all biopolymers, ribonucleic acids or RNA have unique functional versatility, which led to the early suggestion that RNA alone (or a closely related biopolymer) might have once sustained a primitive form of life based on a single type of biopolymer. This has been supported by the demonstration of processive RNA-based replication and the discovery of 'riboswitches' or RNA switches, which directly sense their metabolic environment. In this paper, we further explore the plausibility of this 'RNA world' scenario and show, through synthetic molecular design guided by advanced RNA simulations, that RNA can also perform elementary regulation tasks on its own. We demonstrate that RNA synthetic regulatory modules directly inspired from bacterial transcription attenuators can efficiently activate or repress the expression of other RNA by merely controlling their folding paths 'on the fly' during transcription through simple RNA-RNA antisense interaction. Factors, such as NTP concentration and RNA synthesis rate, affecting the efficiency of this kinetic regulation mechanism are also studied and discussed in the light of evolutionary constraints. Overall, this suggests that direct coupling among synthesis, folding and regulation of RNAs may have enabled the early emergence of autonomous RNA-based regulation networks in absence of both DNA and protein partners.
Dawid
Alexandre
A
Institut Curie, Research Division, CNRS UMR168, 11 rue P. & M. Curie, 75005 Paris, France.
Cayrol
Bastien
B
Isambert
Hervé
H
D001419:Bacteria / Q000201:enzymology / Q000235:genetics*; D001483:Base Sequence; D012321:DNA-Directed RNA Polymerases / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D009690:Nucleic Acid Conformation; D016372:RNA, Antisense / Q000138:chemical synthesis / Q000737:chemistry* / Q000235:genetics*; D012329:RNA, Bacterial / Q000138:chemical synthesis / Q000737:chemistry* / Q000235:genetics*; D014158:Transcription, Genetic
D029968:Escherichia coli Proteins; D016372:RNA, Antisense; D012329:RNA, Bacterial; D012321:DNA-Directed RNA Polymerases