Protein Homochirality May Be Derived from Primitive Peptide Synthesis by RNA

Abstract

Homochirality is a feature of life, but its origin is still disputed. Recent theories indicate that the origin of homochirality coincided with that of the RNA world, but proteins have not yet been incorporated into the story. Ribosome is considered a living fossil that survived the RNA world and records the oldest interaction between RNA and proteins. Inspired by several ribosome-related findings, we propose a hypothesis as follows: the substrate chirality preference of some primitive peptide synthesis ribozymes can mediate the chirality transmission from RNA to protein. In return, the chiral preference of protective peptide-RNA interaction can bring these ribozymes an evolutionary advantage and facilitate the expansion of enantiomeric excess in peptides. Monte Carlo simulation results show that this system's chemistry model is plausible. This model can be further tested through investigation of the chirality preference for the interactions between d/l-ribose-composed rRNA homologs and l/d-amino acid-composed peptides.

1. Introduction

Homochirality is a significant feature of life. Only one of two enantiomers of chiral sugars and amino acids was used to build biological macromolecules such as RNA, DNA, and proteins. The origin of homochirality has attracted scientists' attention for more than a century. Many theories probing this issue attribute it to asymmetrical physical and chemical factors that may cause the symmetry break in the chiral small molecules. However, these theories are not faultless due to the weak effects or harsh preconditions for the physical and chemical factors (Blackmond, 2019). Other theories proposed that homochirality was achieved during the formation of biological macromolecules. RNA has always been a research focus of prebiotic chemistry, because of its catalysis and replication capabilities. The RNA world hypothesis (Crick, 1968; Orgel, 1968; Gilbert, 1986; Higgs and Lehman, 2015) could be one of widely accepted scenarios for the origin of life. The chirality of RNA is derived from its component sugar, that is, ribose. Meteorites/impactors may have brought ribose to Earth (Furukawa et al., 2019); excesses of the d-form sugars have been observed in multiple meteorite samples (Cooper and Rios, 2016), which implies that extraterrestrial ribose may have caused slight enantiomer excesses in the materials for RNA synthesis. A phenomenon observed in RNA replication is that the template-directed oligomerization can be inhibited by a “wrong-handed” nucleotide (Frank, 1953). This property, referred to as enantiomeric cross-inhibition, has been thought to result in the homochirality in RNA. Sandars (2003) created a model that describes the polymerization of a pair of chiral monomers in which the polymerization of one kind of monomers can be stopped by a monomer with another chirality. In this model, enantiomeric cross-inhibition was found to drive the chirality bifurcation and lead to the homochirality in polymers. Some subsequent studies also supported this opinion (Brandenburg et al., 2005; Wattis and Coveney, 2005). Recently, based on the RNA world scenario, Chen and Ma performed Monte Carlo simulations to investigate the chirality deviation in RNA replication (2020). They also found that enantiomeric cross-inhibition is the key factor to amplify the slight enantiomer excesses that initially existed within an RNA replication system. Based on these findings, it can be speculated that an RNA world may achieve homochirality through RNA intrinsic properties.

Compared with RNA, proteins are difficult to self-replicate, and there is no enantiomeric cross-inhibition in the nonenzymatic polymerization of amino acids. Therefore, although the meteorites also brought excess l-amino acids (Cronin and Pizzarello, 1997; Elsila et al., 2016), proteins are unlikely to achieve homochirality in the same way as RNA (although other ways to homochirality may exist, as reviewed by Blackmond, 2019). However, recent perspectives have suggested that peptides may be produced in the RNA world and play important roles therein (Preiner et al., 2020), which implied an alternative possibility: the homotypic chirality of protein was derived from RNA.

Some earlier studies found that d-ribose-contained RNA prefer to bind and react with l-amino acids (Lacey et al., 1988, 1992, 1993) and even have a preference to catalyzing the synthesis of l-amino-acid peptides (Lacey et al., 1990). Sandars argued that these preferences did not develop into a homochirality in amino acids or proteins because they may not have been available in the prebiotic environment, and these preferences cannot guarantee the nonlinear expansion of enantiomeric excess, which could be a problem in achieving homochirality (2005). Sandars suggested that the homochirality of proteins may have been achieved at a later stage of evolution, because the primitive protein translation system may have had no preference for amino acid chirality (2005). In Sandars' scenario, proteins were translated in proto-cells by a refined translation system in which RNA codons could distinguish different enantiomers of amino acids. Because homochirality facilitates the formation of secondary structures such as α-helices and β-sheets and further improves the protein functions, proto-cells that use translation systems that produce homochirality proteins and biosynthetic pathways for single enantiomers of amino acids would dominate in survival competition. The two crucial points of this scenario are the evolutionary advantages of proteins' homochirality and the self-replicating ability of the RNA codons, which are the bearer of chirality information. The former can trigger the symmetry break in proteins, and the latter can drive the initial small asymmetry to homochirality in a nonlinear way. However, although this scenario is intriguing and at least as reasonable as other homochirality origin theories, it relies on a genetic system with coding and decoding functions and cells that approximate modern ones, while these complex systems were considered to have originated at a later stage of protein synthesis system evolution (Fox, 2010; Petrov et al., 2015) and may not have been available before the homochirality proteins.

Is there a simpler system that also can fulfil both critical points in Sandars' theory? Some recent findings with regard to ribosome function have shown that the chirality transmission from RNA to protein may have occurred earlier than the origin of genetic codons and been carried out by the primitive simple protein synthesis system. In this paper, we review these studies and propose a systems chemistry model in which the chiral preference of peptide synthesis and protective peptide binding mediate the chirality transmission from RNA to protein.

2. Ribosome and Its Chiral Preference of Substrates

Ribosome, as the core of protein translation, could be a molecular fossil that reveals the early interactions between RNA and proteins (Harish and Caetano-Anollés, 2012; Petrov et al., 2015) and may also contain clues about the chirality transmission between them. The modern ribosome is composed of a small subunit (SSU) that mainly carries out codon recognition that cooperates with tRNA's bottom half; the ribosome's large subunit (LSU), however, catalyzes peptide bond formation and cooperates with tRNA's top half. The early evolution of LSU and SSU is deduced to have been a separate process, and so were the two parts of the tRNA (Fox, 2010; Petrov et al., 2015). The most ancient part of the ribosome was supposed to be the rRNA in the peptidyl transferase center (PTC) locating at LSU where the peptide bond synthesis occurs (Fox, 2010; Petrov et al., 2015). The tRNA top half can form a minihelix structure alone that can attach amino acids, and its CCA tail that directly attaches to amino acids is extremely conserved in the phylogenetic tree. Therefore, the tRNA top half is considered to be older than the bottom half (Fox, 2010). These findings depict a scenario for the primitive enzymatic peptide synthesis system (protein may not be available at the time) in which PTC-RNA-like ribozymes catalyze the condensation of amino acids with the help of the CCA-tailed proto-tRNA, while the coding and decoding components of modern translate system (mRNA, SSU, and tRNA bottom half) were not yet integrated into the system (Petrov et al., 2015).

Modern biological peptide synthesis is a two-step process. Amino acids are first attached to the CCA tails of the tRNA top half through the aminoacylation reaction. Then, the generated aminoacyl-tRNA enters the ribosome, and the condensation of amino acids occurs in the PTC. Both aminoacylation and PTC-catalyzed condensation have preferences for the chirality of the substrate. Tamura and Schimmel (2006) performed a nonenzymatic aminoacylation reaction between a phosphate oligonucleotide-modified alanine and an RNA minihelix that imitates the ancient tRNA top half. In the experiment, the reaction efficiency of l-alanine was approximately four-fold higher than that of d-alanine when the RNA was composed of d-ribose nucleotides, while the mirror-image experiment showed an opposite preference. The subsequent molecular dynamics simulations revealed that this preference is related to the relative situation between the side chain of alanine and the 3'-OH of the ribose of the adenylate at the end of the CCA tail (Ando et al., 2018). The d-alanine side chain is located too close to the OH, which thus hinders its reaction with the carbonyl of the oligonucleotide-modified alanine.

Recently, PTC-catalyzed peptide bond formation of d-proline was found to be 50 times slower than l-proline at pH 7.5 (Lehmann and Ye, 2019; Liljeruhm et al., 2019). This preference was also related to the ribose of the adenylate at the end of the CCA tail. The 2'-OH of this ribose of the P-site tRNA works as a proton shuttle during the nucleophilic attack from the amino group of d-amino acids. The amino group is located too far from this OH and is unfavorably oriented, which thus reduces the speed of the condensation reaction (Liljeruhm et al., 2019). Moreover, below-physiological pH levels are proposed to expand this difference (Johansson et al., 2011). The early ocean was inferred to be acidic, with a pH as low as 6.2 at 4.0 Ga (Krissansen-Totton et al., 2018), and thus we think that the chirality transmission may be facilitated in the prebiotic world.

3. A Systems Chemistry Model for Protein Homochirality Origin

The tRNA CCA tail and PTC rRNA originated very early, so the above-mentioned two kinds of chiral preferences of substrates may have also existed in the primitive peptide synthesis system and enabled chirality transmission from RNA to peptides. Inspired by these findings, we propose a systems chemistry model for the origin of protein homochirality (Fig. 1) as follows: the primitive peptide synthesis system consisting of CCA-tailed proto-tRNA and PTC RNA-like ribozymes prefers l-enantiomer of amino acids as substrates, which induces a chirality imbalance in synthesized peptides. The replication of proto-tRNA and PTC RNA-like ribozymes provides the prerequisites to the rapid amplification of this imbalance.

FIG. 1.

A systems chemistry model for the origin of protein homochirality. In a preexisting d-ribose-RNA-predominant world, systems composed of proto-tRNAs and ribozymes can synthesize peptides and replicate themselves. There may have been peptide synthesis systems that prefer l-amino acids, d-amino acids, or have no preference for substrate chirality. These three peptide synthesis systems are represented by the orange, blue, and green lines, respectively. Proto-tRNA and peptide synthesis ribozymes that prefer l-amino acids may be the homologs of the modern CCA-tailed tRNA and PTC RNA, respectively. Peptides containing only l-amino acids are assumed to bind more readily with d-ribose-RNA and protect the latter from degradation. Thus, ribozymes that synthesize l-peptides have a higher chance to become replication templates. This evolutionary advantage may result in their dominance in the population. This positive feedback in the system facilitates the transmission of chirality from RNA to proteins.

In our model, RNA is the bearer of chirality information in a different way from Sandars' theory. RNA implements this function through substrate selectivity instead of working as codons. RNA's self-replicate ability can enable the nonlinear expansion of enantiomeric excess. It is noteworthy that the early evolution of codon recognition and peptide synthesis could be separate. The integration of the two functions may have occurred at a later stage of peptide synthesis system evolution (Petrov et al., 2015). The independence of the coding and decoding functions means that our model can make chirality transmission occur in an earlier and simpler peptide synthesis system.

It has been found that introducing mutations in the PTC and/or its adjacent regions can elevate the use of d-amino acids of ribosome (Starck et al., 2003; Tan et al., 2004; Dedkova et al., 2006), and d-amino acids can also attach to tRNA homologs (Tamura and Schimmel, 2006). These findings imply that there may have been ancient protein synthesis systems that had no preference for substrate chirality or had preference for d-amino acids, which raises a question our model needs to answer: why did the ancestor of the modern translation system prefer to use l-amino acids?

A reasonable answer to this question is that chiral preference of substrates can bring an evolutionary advantage to the peptide synthesis system. In Sandars' theory, proto-cells with a protein synthesis system that produces homochiral proteins survived the competition because homochirality improved the protein functions by facilitating the formation of secondary structures (2005). As discussed before, this theory relies on complex systems that were unlikely available before the achievement of homochirality. Fox (2010) also supposed that the exclusive requirements for substrate chirality of the modern ribosome are the result of selection, but did not explain how producing homochirality can bring advantages in evolution.

Here, we suggest that an evolutionary advantage may be achieved by the protection of peptides on RNA with a chiral preference. The concept that peptides can protect RNA was presented in the work of Szostak, who suggested that short peptides containing acidic residues play a very important role in protecting RNA molecules against Mg²⁺-induced degradation by chelating these ions (2012). Mg²⁺ is ubiquitous in the environment and has been found to help the LSU rRNA collapse into a native structure (Van der Gulik and Speijer, 2015; Lenz et al., 2017). The modern ribosome's peptidyl transferase activity is also based on Mg²⁺ (Miskin et al., 1970). Therefore, it is reasonable to assume that peptides were employed by the ancient PTC RNA-like ribozymes to maintain their stability. Moreover, binding with peptides can reduce the chance of being attacked by water molecules, which is a major cause of biomolecule degradation (Bains et al., 2015). Interestingly, rRNA was proposed to function prebiotically as mRNA and code its protector proteins (Root-Bernstein and Root-Bernstein, 2015, 2016). If so, the rRNA-coded proteins may replace the protective peptides, which were used by the primitive synthesis system after the integration of coding and decoding components.

We further assume that the peptide-RNA interaction (PRI) has a chiral preference. No reports have been found to directly support this assumption, but some observations have shown that d-ribose-RNA tend to bind l-amino acids. Root-Bernstein (2007, 2010) observed that d-trinucleotides bind preferentially with l-amino acids rather than d-amino acids, while l-trinucleotides show the reverse preference. Using a racemic mixture of histidine as a bait, Illangasekare et al. (2010) selected d-ribose-RNA aptamers in a 10¹⁴∼10¹⁵ library. After the selection, most of the obtained RNA aptamers were found to tend to bind l-histidine. These findings suggest that d-ribose-RNA may prefer to bind peptides that consist of l-amino acids.

For the primitive PTC RNA-like ribozymes, peptides synthesized by themselves were naturally the first choice for protectors. If the interaction between them also had a chiral preference as we assume, ribozymes that synthesize peptides with l-amino acids would be better protected than the counterparts that synthesize peptides with another or hybrid chirality. Ribozymes under the protection of peptides have a higher chance of becoming replication templates, generating a positive feedback loop in the system and facilitating the transmission of chirality (Fig. 1).

4. Monte Carlo Simulations

To verify whether the chiral preference of protective PRI can bring an evolutionary advantage to the peptide synthesis systems that produce peptides with l-amino acids, Monte Carlo simulations were performed (Fig. 2). The components of the simulation system are listed in Table 1. In the simulation process, several simplifications and assumptions were made: (i) As discussed above, homochirality may have been first achieved in RNA. Therefore, all the RNA components in the simulation were considered to be d-ribose-RNA. (ii) Amino acids were divided into d-amino acids and l-amino acids, and their amounts are unlimited. (iii) The “peptide synthesis unit” (PSU) was used to represent the functions of catalyzing aminoacylation and peptide bond formation in the speculative primitive peptide synthesis system, which was assumed to be able to unlimitedly replicate. According to our model, the chirality transmission occurred before the origin of genetic codons, so PSU does not have coding and decoding functions. (iv) As discussed above, there may have been peptide synthesis systems that had no preference for substrate chirality or preference for d-amino acids. Therefore, the PSU population consists of l-PSU that use l-amino acids as substrates, d-PSU that use d-amino acids as substrates, and r-PSU that have no preference for substrate chirality. (v) Theoretically, r-PSU can produce peptides that contain different ratios of the two amino acid enantiomers. For peptides composed of two enantiomers, regardless of the ratios, they were considered to have the same properties. (vi) PSU only interacts with the peptides synthesized by itself, because of their relative spatial adjacency. In each Monte Carlo step of the simulation, PSU had chances to synthesize peptides, interact with their synthesized peptides to form complexes, degrade, and replicate. The parameters describing the probability of these events with specific values are listed in Table 1.

FIG. 2.

Monte Carlo simulation procedure. The simulated system is composed of peptide synthesis units (PSU), peptides, and the complex of PSU and peptides. These components are linked by the events that occurred in the simulation (arrows). Descriptions of these components and events are listed in Table 1. In one simulation step, these events go through in the following order: peptide synthesis, complex formation, degradation, and replication. The simulation is implemented in Python 3.6, and the corresponding script can be found at https://github.com/xychu-cyber/Homochirality-Origin.

Table 1.

Description of Monte Carlo Simulation System

Compositions	Descriptions	Initial values
l-PSU	Peptide synthesis unit using l-amino acids as substrates	1
d-PSU	Peptide synthesis unit using d-amino acids as substrates	1
r-PSU	Peptide synthesis unit has no preference for substrate chirality	1, 10¹⁰
l-peptide	Peptides composed entirely of l-amino acids	0
d-peptide	Peptides composed entirely of d-amino acids	0
r-peptide	Peptides composed of mixed l/d-amino acids	0
l-l-complex	Complex of l-PSU and l-peptide	0
d-d-complex	Complex of d-PSU and d-peptide	0
r-l-complex	Complex of r-PSU and l-peptide	0
r-d-complex	Complex of r-PSU and d-peptide	0
r-r-complex	Complex of r-PSU and r-peptide	0
Probabilities	Descriptions	Values^*
P _{syn_LL}	The probability of l-PSU synthesizing l-peptide	0.5
P _{syn_DD}	The probability of d-PSU synthesizing d-peptide	0.5
P _{syn_RL}	The probability of r-PSU synthesizing l-peptide	0.005
P _{syn_RD}	The probability of r-PSU synthesizing d-peptide	0.005
P _{syn_RR}	The probability of r-PSU synthesizing r-peptide	0.99
P _{bind_L}	The probability of PSU being bound by its synthesized l-peptide	0.01, 0.03, 0.06, 0.1
P _{bind_D}	The probability of PSU being bound by its synthesized d-peptide	0.01
P _{bind_R}	The probability of PSU being bound by its synthesized r-peptide	0.01
P _{deg_psu}	The probability of PSU degradation	0.5
P _{deg_com}	The probability of PSU-peptide complex degradation	0.05, 0.1, 0.25, 0.5
P _rep	The probability of PSU replication	1

Because most peptides synthesized by r-PSU contain both amino acid enantiomers, P _{syn_RR} was set much higher than P _{syn_RL} and P _{syn_RD}. The three parameters indicate the possibility of synthesizing r-, l- and d-peptides, respectively. For l-PSU and d-PSU, only half of the amino acids can be used; their probabilities to synthesize peptides (P _{syn_LL} and P _{syn_DD}) were set to be half of the sum of P _{syn_RR}, P _{syn_RL}, and P _{syn_RD}. The chiral preference of PRI is characterized by the differences among the parameters P _{bind_R}, P _{bind_D}, and P _{bind_L}, which represent the possibility that r-, d-, and l-peptides bind with PSU, respectively. The protective effect is characterized by the difference between the parameters P _{deg_psu} and P _{deg_com}, which represent the possibility of the degradation of PSU and PSU-peptide complex. Our model is premised on an RNA world, where ribozymes should be able to maintain certain population size. Therefore, the replication possibility (P _rep) of PSU should be balanced with its degradation possibility, which means that without the protection of the peptide, the population of PSU remains unchanged.

We first assumed that the three PSUs accounted for the same proportion in the initial population and compared the changes of PSU population composition under different PRI chiral preference degrees and protective effects. When the protective effect does not exist, that is, the peptide-PSU complex degrades as readily as PSU (P _{deg_psu} = P _{deg_com} = 0.5), the population and composition of PSUs remain the initial values during the 1000-step simulation, no matter how the chiral preference of PRI changes (Fig. 3A). However, when the peptide can protect PSU (P _{deg_psu} = 0.5, P _{deg_com} = 0.05), and l-peptide has higher possibilities to bind PSU (P _{bind_L} > P _{bind_D} = P _{bind_R} = 0.1), the ratios of l-PSU increase in nonlinear ways and eventually replace other PSUs almost completely (Fig. 3A). The stronger the protection, the faster the l-PSU increase. The ratios of l-peptides exhibited similar, though delayed, growth patterns (Fig. 3B). Interestingly, if the PRI has no chiral preference (P _{bind_R} = P _{bind_D} = P _{bind_L} = 0.1) but the peptide can protect PSU, the ratios of l-PSU and d-PSU (d-PSU not shown in the figure) and their products reduced to ∼0 in the simulation (Fig. 3A, 3B) because r-PSU can use a wider range of substrates to produce more protective peptides and thus become dominant.

FIG. 3.

Monte Carlo simulation results. The horizontal axis represents Monte Carlo simulation steps. Lines represent the ratios of l-PSU (A and C) and l-peptide (B and D). In all simulations, P _{bind_D} = P _{bind_R} = 0.01, P _{deg_psu} = 0.5. The initial ratios of l-PSU, d-PSU, and r-PSU were set to be 1:1:1 (A and B) and 1:1:10¹⁰ (C and D). P _{bind_L} > 0.01 represents l-peptide has a higher possibility to bind PSU than d- and r-peptides, which means a chiral preference exists in PRI. P _{deg_com} < 0.5 represents PSU-peptide complex is more stable than PSU, which means that peptide can protect RNA.

According to the opinions of Sandars (2005) and Fox (2010), most of the early peptide synthesis ribozymes may not distinguish the chirality of amino acids. To simulate this situation, the initial ratio of l-PSU, d-PSU, and r-PSU was set to 1:1:10¹⁰. The different combinations of PRI chiral preference degrees and peptide protective effects were also tested. Consistent with the above simulation, if l-peptides bind and protect PSU more readily than other kinds of peptides, the ratio of l-PSU and l-peptide will increase to ∼1. Higher PRI chiral preference and stronger peptide protective effect lead to earlier and faster increase (Fig. 3C, 3D). These results indicate that the peptide protective effect with chiral preference can bring an evolutionary advantage to the peptide synthesis system by producing homochiral peptides and make it dominant in the population. Along with this process, the synthesized peptides also reach homochirality.

5. Discussion

In summary, the present model provides a plausible scenario of chirality transmission from RNA to peptides. This scenario assumes the preexistence of a homochiral d-ribose-RNA world, in which ribozymes could synthesize peptides and replicate themselves. Among ribozyme-based primitive peptide synthesis systems, those that prefer l-amino acids as substrates have a higher probability to be bound and protected by the synthesized peptides, because l-amino acid-composed peptides tend to bind d-ribose-RNA. Peptides' protection brings an evolutionary advantage to these RNAs so that they can be utilized by the common ancestor of modern life and preserved in the form of ribosomal PTC RNA and tRNA. The main assumption in this scenario is the chiral preference in the protection of peptides on ribozymes, which can be divided into two aspects: ribozymes utilized peptides as protectors, and this protection has a chiral preference. The results of Monte Carlo simulations show that both aspects are necessary for the peptide synthesis system to gain an advantage in evolution and thus achieve the homochirality in peptides. Compared with the previous theory proposed by Sandars, our scenario relies on a simpler system and is based on the recognized characteristics of ribosomes.

Traces of the ancient protective peptides may remain in the modern ribosome. Most universal ribosome proteins (rProteins) are composed of globular domains arranged on the ribosomal surface and random coil tails extended into the core near the PTC (Kovacs et al., 2017). The tails may have had an earlier origin than the rest of the rProteins. The rProtein L2 in LSU is one of the oldest rProteins, and its tail is the protein component closest to PTC (Kovacs et al. 2017). L2 tail was found to interact with a magnesium microcluster, while the latter also interacts with PTC (Petrov et al., 2012). These findings suggest that rProtein tails may root in the ancient protective peptides that bind PTC RNA homologs, and the ancient RNA protector peptides may also lack fixed structures. Fox (2010) suggested that, in the primitive ribosome, the corresponding components of the rProtein tails could have been partially chiral peptides (peptides containing more l-amino acids than d-amino acids), which could not form structures like α-helix or β-sheet. In our simulation, partially chiral peptides were considered to have different properties from homochiral peptides; whether they can bind and protect RNA deserve further studies.

In the present study, we assume that protein synthesis relies on RNA, which follows the opinion of RNA world theory and is consistent with what happens in all existing organisms, but also means that chirality is directionally transferred from RNA to protein. However, RNA may not have been necessary for small protein synthesis in the primitive world (Canavelli et al., 2019). Recently, Skolnick et al. (2019) proposed a scenario of protein homochirality origin in which RNA was not involved. They found that homochiral proteins have longer secondary structures and are thermodynamically more stable than the proteins built from amino acids of mixed chirality, and thus homochiral proteins can be retained in natural selection. Interestingly, some of the most ancient protein structures such as P-loop can bind RNA (Romero et al., 2018), which suggests an ancient origin of PRI that may have been earlier than the establishment of the homochirality of the RNA world. Combined with the protection of peptides on RNA, these findings imply a possibility that the chirality of protein may also have been transferred to RNA. The abundance of different enantiomers of peptides may also have shaped the chirality preference of the primitive peptide synthesis system and even affected the RNA world's choice of chirality. This bidirectional influence between RNA and peptides can form a positive feedback loop, which amplifies the initial slight chirality imbalance and eventually achieves homochirality. Root-Bernstein (2007, 2010) suggested a similar concept, in which the main players are RNA trinucleotide codons and amino acids. Nevertheless, the chiral preference in RNA-amino acid interaction has not been demonstrated to be prevalent in all amino acids, nor has it been demonstrated as to whether it can affect the RNA-peptide interactions. To test our model, the chirality preference of RNA-peptide interactions will require further investigation, in particular examination of those interactions among l/d-ribose-composed PTC RNA homologs and d/l-amino acid-composed peptides.

Footnotes

Acknowledgments

This work was supported by the National Natural Science Foundation of China (31870837).

Author Disclosure Statement

The authors declare that they have no competing financial interests.

Abbreviations Used

Associate Editor: Norman Sleep

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