A simple physical mechanism enables homeostasis in primitive cells

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)448-453
Number of pages6
JournalNature Chemistry
Volume8
Issue number5
DOIs
StatePublished - May 1 2016

Fingerprint

Catalytic RNA
Oligonucleotides
RNA
Dilution
MicroRNAs
Fatty acids
Catalysis
Fatty Acids
Chemical activation

Cite this

A simple physical mechanism enables homeostasis in primitive cells. / Engelhart, Aaron E.; Adamala, Katarzyna P.; Szostak, Jack W.

In: Nature Chemistry, Vol. 8, No. 5, 01.05.2016, p. 448-453.

Research output: Contribution to journalArticle

@article{578c379de40c437988101b2a138a6ac2,
title = "A simple physical mechanism enables homeostasis in primitive cells",
abstract = "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.",
author = "Engelhart, {Aaron E.} and Adamala, {Katarzyna P.} and Szostak, {Jack W.}",
year = "2016",
month = "5",
day = "1",
doi = "10.1038/nchem.2475",
language = "English (US)",
volume = "8",
pages = "448--453",
journal = "Nature Chemistry",
issn = "1755-4330",
publisher = "Nature Publishing Group",
number = "5",

}

TY - JOUR

T1 - A simple physical mechanism enables homeostasis in primitive cells

AU - Engelhart, Aaron E.

AU - Adamala, Katarzyna P.

AU - Szostak, Jack W.

PY - 2016/5/1

Y1 - 2016/5/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84964426871&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84964426871&partnerID=8YFLogxK

U2 - 10.1038/nchem.2475

DO - 10.1038/nchem.2475

M3 - Article

C2 - 27102678

AN - SCOPUS:84964426871

VL - 8

SP - 448

EP - 453

JO - Nature Chemistry

JF - Nature Chemistry

SN - 1755-4330

IS - 5

ER -