“…Thus, hydrophobic-cationic peptide aggregates can accumulate RNA (and NTPs to a lesser extent) on their surfaces in low ionic strength conditions and reactivate/enhance ribozyme activities in high ionic strength conditions. Such a mechanism might also have supported the accumulation and activation of ribozymes in the fluctuating environments of the prebiotic earth (e.g., temperature, solute concentrations) 38 – 41 . Fig.…”
Section: Resultsmentioning
confidence: 99%
“…Our results also suggest the potential beneficial roles of hydrophobic-cationic peptide aggregates in the emergence of RNA-based life. On the primordial earth, the environment surrounding the primitive biopolymers would have inevitably fluctuated (e.g., temperature, solute concentrations, ionic strength), and the capacity of biopolymers to survive under a variety of such conditions would have likely been critical 38 – 41 , 48 – 55 . Hydrophobic-cationic peptides could have become concentrated as aggregates without dissipating and such aggregates could have accumulated scarce nucleotides and RNA molecules on their surfaces and prevented them from being washed away (e.g., by rainfall, flowing water).…”
Accretion and the resulting increase in local concentration is a widespread mechanism in biology to enhance biomolecular functions (for example, in liquid-liquid demixing phases). Such macromolecular aggregation phases (e.g., coacervates, amyloids) may also have played a role in the origin of life. Here, we report that a hydrophobic-cationic RNA binding peptide selected by phage display (P43: AKKVWIIMGGS) forms insoluble amyloid-containing aggregates, which reversibly accrete RNA on their surfaces in an RNA-length and Mg2+-concentration dependent manner. The aggregates formed by P43 or its sequence-simplified version (K2V6: KKVVVVVV) inhibited RNA polymerase ribozyme (RPR) activity at 25 mM MgCl2, while enhancing it significantly at 400 mM MgCl2. Our work shows that such hydrophobic-cationic peptide aggregates can reversibly concentrate RNA and enhance the RPR activity, and suggests that they could have aided the emergence and evolution of longer and functional RNAs in the fluctuating environments of the prebiotic earth.
“…Thus, hydrophobic-cationic peptide aggregates can accumulate RNA (and NTPs to a lesser extent) on their surfaces in low ionic strength conditions and reactivate/enhance ribozyme activities in high ionic strength conditions. Such a mechanism might also have supported the accumulation and activation of ribozymes in the fluctuating environments of the prebiotic earth (e.g., temperature, solute concentrations) 38 – 41 . Fig.…”
Section: Resultsmentioning
confidence: 99%
“…Our results also suggest the potential beneficial roles of hydrophobic-cationic peptide aggregates in the emergence of RNA-based life. On the primordial earth, the environment surrounding the primitive biopolymers would have inevitably fluctuated (e.g., temperature, solute concentrations, ionic strength), and the capacity of biopolymers to survive under a variety of such conditions would have likely been critical 38 – 41 , 48 – 55 . Hydrophobic-cationic peptides could have become concentrated as aggregates without dissipating and such aggregates could have accumulated scarce nucleotides and RNA molecules on their surfaces and prevented them from being washed away (e.g., by rainfall, flowing water).…”
Accretion and the resulting increase in local concentration is a widespread mechanism in biology to enhance biomolecular functions (for example, in liquid-liquid demixing phases). Such macromolecular aggregation phases (e.g., coacervates, amyloids) may also have played a role in the origin of life. Here, we report that a hydrophobic-cationic RNA binding peptide selected by phage display (P43: AKKVWIIMGGS) forms insoluble amyloid-containing aggregates, which reversibly accrete RNA on their surfaces in an RNA-length and Mg2+-concentration dependent manner. The aggregates formed by P43 or its sequence-simplified version (K2V6: KKVVVVVV) inhibited RNA polymerase ribozyme (RPR) activity at 25 mM MgCl2, while enhancing it significantly at 400 mM MgCl2. Our work shows that such hydrophobic-cationic peptide aggregates can reversibly concentrate RNA and enhance the RPR activity, and suggests that they could have aided the emergence and evolution of longer and functional RNAs in the fluctuating environments of the prebiotic earth.
“…1A, Figure S1). While the low pH conditions enable transient melting of otherwise stable nucleic acid duplexes, the co-accumulation of RNA and magnesium ions at water-gas interfaces by capillary ow promotes folding and catalysis 22,23 .…”
The replication of nucleic acids is a prerequisite for the survival and evolution of living systems. Before the advent of protein synthesis, genetic information was most likely stored on and replicated by RNA. However, experimental systems for sustained RNA-dependent RNA-replication are difficult to realise due to the high thermodynamic stability of duplex products and the low chemical stability of catalytic polynucleotides. Using a derivative of a group I intron as a model for an RNA replicase, we show that heated air-water interfaces exposed to a plausible CO2-rich atmosphere drive complete cycles of plus and minus strand replication. The reaction is driven by autonomous oscillations in salt concentrations and pH that transiently destabilise RNA duplexes. Newly synthesised strands can dissociate from their templates and adopt catalytically active conformations. Our results suggest that an abundant Hadean microenvironment may have promoted the replication of RNAs while maintaining the activity of the synthesised ribozymes.
“…This system has recently been shown to be active in the presence of poly(L-lysine) under certain conditions, and so was a promising starting point when considering compatibility with coacervate systems 14 . We previously redesigned the ribozyme-substrate complex to iteratively produce long RNA concatemers from short oligonucleotides 42 . In our final design, the ribozyme (E L ) catalyses concatenation of a 31 nt substrate ( Figure 1a ).…”
Condensed coacervate phases are now understood to be important features of modern cell biology, as well as valuable protocellular models in origin of life studies and synthetic biology. In each of these fields, the development of model systems with varied and tuneable material properties is of great importance for replicating properties of life. Here, we develop a ligase ribozyme system capable of concatenating short RNA fragments into extremely long chains. Our results show that formation of coacervate microdroplets with the ligase ribozyme and poly(L-lysine) enhances ribozyme rate and yield, which in turn increases the length of the anionic polymer component of the system and imparts specific physical properties to the droplets. Droplets containing active ribozyme sequences resist growth, do not wet or spread on unpassivated surfaces, and exhibit reduced transfer of RNA between droplets when compared to controls containing inactive sequences. These altered behaviours, which stem from RNA sequence and catalytic activity, constitute a specific phenotype and potential fitness advantage, opening the door to selection and evolution experiments based on a genotype – phenotype linkage.
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