Triplet-Encoded Prebiotic RNA Aminoacylation

Su, Meng; Schmitt, Christian; Liu, Ziwei; Roberts, Samuel J.; Liu, Kim C.; Röder, Konstantin; Jäschke, Andres; Wales, David J.; Sutherland, John D.

doi:10.1021/jacs.3c03931

Cited by 14 publications

(16 citation statements)

References 46 publications

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“…Combining this selection mechanism with the prebiotic availability of amino acids produced by the cyanosulfidic scenario would explain why glycine, alanine, valine, leucine, serine, threonine, arginine, and proline are all assigned to family-box codons in modern biology. In light of our recent work on coded aminoacylation, which family-box codons code for each amino acid would be dependent on the fusion of acceptor stems and anticodon domains. It is possible that the precise relationship between any particular family-box codon and its encoded amino acid is a “frozen accident” …”

Section: Discussionmentioning

confidence: 99%

“…Our recent finding that the terminal trinucleotide sequence of a tRNA acceptor stem analogue influences the specificity and stereochemistry of 3′-terminal aminoacylation suggests that loosely coded aminoacyl-tRNA acceptor stem-overhang domains could have been produced by prebiotic chemistry. , However, the degree of intrinsic coding is low, and we suspect that higher fidelity coding is unlikely without extrinsic auxiliary control elements such as ribozymes. To us, this implies that if the initial loosely coded aminoacyl-tRNAs had participated in the early stages of ribosomal peptide synthesis, the short peptides thus produced would not have been advantageous to the system per se.…”

Section: Introductionmentioning

confidence: 97%

“…If such recognition took place, parsimony suggests that it should have been between the amino acid residue and the anticodon, but this is countered by the fact that the 3′-terminal aminoacylation site is some 75 Å distant from the anticodon. Having a trinucleotide sequence elsewhere in the tRNA acting as the aminoacylation specificity control element alleviates this distance constraint but decouples the nature of the aminoacyl residue and the sequence of the anticodon, necessitating an alternate mechanism for amino acid–codon assignments.…”

Section: Introductionmentioning

confidence: 99%

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Initial Amino Acid:Codon Assignments and Strength of Codon:Anticodon Binding

Su,

Roberts,

Sutherland

2024

J. Am. Chem. Soc.

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The ribosome brings 3′-aminoacyl-tRNA and 3′-peptidyl-tRNAs together to enable peptidyl transfer by binding them in two major ways. First, their anticodon loops are bound to mRNA, itself anchored at the ribosomal subunit interface, by contiguous anticodon:codon pairing augmented by interactions with the decoding center of the small ribosomal subunit. Second, their acceptor stems are bound by the peptidyl transferase center, which aligns the 3′-aminoacyl-and 3′-peptidyl-termini for optimal interaction of the nucleophilic amino group and electrophilic ester carbonyl group. Reasoning that intrinsic codon:anticodon binding might have been a major contributor to bringing tRNA 3′-termini into proximity at an early stage of ribosomal peptide synthesis, we wondered if primordial amino acids might have been assigned to those codons that bind the corresponding anticodon loops most tightly. By measuring the binding of anticodon stem loops to short oligonucleotides, we determined that family-box codon:anticodon pairings are typically tighter than split-box codon:anticodon pairings. Furthermore, we find that two family-box anticodon stem loops can tightly bind a pair of contiguous codons simultaneously, whereas two split-box anticodon stem loops cannot. The amino acids assigned to family boxes correspond to those accessible by what has been termed cyanosulfidic chemistry, supporting the contention that these limited amino acids might have been the first used in primordial coded peptide synthesis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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Initial Amino Acid:Codon Assignments and Strength of Codon:Anticodon Binding

Su,

Roberts,

Sutherland

2024

J. Am. Chem. Soc.

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“…Die wichtigsten Merkmale unseres Modells sind: 1. Die Reaktion von zwei Aminosäuren, die über die nicht-kanonischen Nukleoside m 6 aa 6 A und mnm 5 Frühere Studien der Forschungsgruppen von Lacey, [25,26] Tamura und Schimmel, [27,28,29,30,31] Sutherland [32,33,34] und Richert [35] zeigten bereits, dass α-Aminosäuren, die an 5'phosphorylierte Nukleotide und RNAs gebunden sind, entweder über die Carbonsäuregruppe als Acylphosphat-Anhydrid, [36] oder mit der α-Aminogruppe in Form von Phosphoramidaten, [37] bevorzugt reagieren, wenn sie L-konfiguriert sind. Wir haben untersucht, wie unser RNA-Peptid-Synthesezyklus (Abbildung 1a) durch die Stereochemie beeinflusst wird.…”

Section: Einführungunclassified

RNA‐Vermittelte Peptidbindungen Fördern die L‐Homochiralität

Węgrzyn,

Mejdrová,

Müller

et al. 2024

Angewandte Chemie

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The world in which we live is homochiral. The ribose units that form the backbone of DNA and RNA are all D‐configured and the encoded amino acids that comprise the proteins of all living species feature an all‐L‐configuration at the α‐carbon atoms. The homochirality of α‐amino acids is essential for folding of the peptides into well‐defined and functional 3D structures and the homochirality of D‐ribose is crucial for helix formation and base‐pairing. The question of why nature uses only encoded L‐α‐amino acids is not understood. Herein, we show that an RNA‐peptide world, in which peptides grow on RNAs constructed from D‐ribose, leads to the self‐selection of homo‐L‐peptides, which provides a possible explanation for the homo‐D‐ribose and homo‐L‐amino acid combination seen in nature.

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“…Previous studies by the research groups of Lacey, [25,26] Tamura and Schimmel, [27,28,29,30,31] Sutherland [32,33,34] and Richert [35] showed already that α-amino acids connected to 5'-phosphorylated nucleotides and RNAs, either via the carboxylic acid group as acyl phosphate mixed anhydrides, [36] or with the α-amino group in the form of phosphoramidates, [37] react preferentially when they are Lconfigured. Herein, we investigated how our RNA-peptide synthesis cycle (Figure 1a) is influenced by stereochemistry.…”

Section: Introductionmentioning

confidence: 99%