A simple physical mechanism enables homeostasis in primitive cells.
The emergence of homeostatic mechanisms that enable maintenance of an intracellular steady state during growth was critical to the advent of cellular life. Here, we show that concentration-dependent reversible binding of short oligonucleotides, of both specific and random sequence, can modulate ribozyme activity. In both cases, catalysis is inhibited at high concentrations, and dilution activates the ribozyme via inhibitor dissociation, thus maintaining near-constant ribozyme specific activity throughout protocell growth. To mimic the result of RNA synthesis within non-growing protocells, we co-encapsulated high concentrations of ribozyme and oligonucleotides within fatty acid vesicles, and ribozyme activity was inhibited. Following vesicle growth, the resulting internal dilution produced ribozyme activation. This simple physical system enables a primitive homeostatic behaviour: the maintenance of constant ribozyme activity per unit volume during protocell volume changes. We suggest that such systems, wherein short oligonucleotides reversibly inhibit functional RNAs, could have preceded sophisticated modern RNA regulatory mechanisms, such as those involving miRNAs.
Department of Molecular Biology, and Center for Computational and Integrative Biology, Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Aaron E
0000-0002-1849-7700
AE
Engelhart
Department of Molecular Biology, and Center for Computational and Integrative Biology, Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.|MIT Media Lab, 77 Massachusetts Avenue, E14/E15, Cambridge, Massachusetts 02139-4307, USA.
Katarzyna P
0000-0003-1066-7207
KP
Adamala
Department of Molecular Biology, and Center for Computational and Integrative Biology, Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Jack W
JW
Szostak
D058045:Artificial Cells / Q000737:chemistry*; D019143:Evolution, Molecular; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry; D006706:Homeostasis; D050178:Monoglycerides / Q000737:chemistry; D009841:Oligonucleotides / Q000737:chemistry; D016337:RNA, Catalytic / Q000037:antagonists & inhibitors / Q000737:chemistry*
D005229:Fatty Acids, Monounsaturated; D050178:Monoglycerides; D009841:Oligonucleotides; D016337:RNA, Catalytic; C427204:hammerhead ribozyme; C054211:9-tetradecenoic acid