Single nucleotide translation without ribosomes

Jash, Biswarup; Tremmel, Peter; Jovanovic, D Marina; Richert, Clemens

doi:10.1038/s41557-021-00749-4

Cited by 40 publications

(38 citation statements)

References 41 publications

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“…This approach, which can be called ‘palaeochemistry’, enabled us to learn about the chemical possibilities that existed in the RNA world and, therefore, sets the chemical framework for the emergence of life. In contrast to earlier investigations of the origin of translation 24 – 29 , we used naturally occurring non-canonical vestige nucleosides and conditions compatible with aqueous wet–dry cycles 30 , 31 .…”

Section: Mainmentioning

confidence: 99%

A prebiotically plausible scenario of an RNA–peptide world

Müller

Escobar

et al. 2022

Nature

108

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The RNA world concept1 is one of the most fundamental pillars of the origin of life theory2–4. It predicts that life evolved from increasingly complex self-replicating RNA molecules1,2,4. The question of how this RNA world then advanced to the next stage, in which proteins became the catalysts of life and RNA reduced its function predominantly to information storage, is one of the most mysterious chicken-and-egg conundrums in evolution3–5. Here we show that non-canonical RNA bases, which are found today in transfer and ribosomal RNAs6,7, and which are considered to be relics of the RNA world8–12, are able to establish peptide synthesis directly on RNA. The discovered chemistry creates complex peptide-decorated RNA chimeric molecules, which suggests the early existence of an RNA–peptide world13 from which ribosomal peptide synthesis14 may have emerged15,16. The ability to grow peptides on RNA with the help of non-canonical vestige nucleosides offers the possibility of an early co-evolution of covalently connected RNAs and peptides13,17,18, which then could have dissociated at a higher level of sophistication to create the dualistic nucleic acid–protein world that is the hallmark of all life on Earth.

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Section: Mainmentioning

confidence: 99%

A prebiotically plausible scenario of an RNA–peptide world

Müller

Escobar

et al. 2022

Nature

108

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“…Indeed, it has been reported that the exocyclic amine of cytidine reacts almost quantitatively with acetic anhydride in an organic solvent such as DMF. 29,30 However, our experiments with 5′-CMP and NAI in aqueous buffer resulted in only 2′- and 3′-regioisomeric ester adducts, as determined by NMR (Fig. S8–S10, ESI†).…”

mentioning

confidence: 84%

“…This might be achieved, for example, in small constrained loop structures. 14,29,30 In modified RNAs, it may also be possible to enhance yield further by designing modified nucleosides having greater acidity at 2 0 -OH.…”

mentioning

confidence: 99%

Conjugation of RNA via 2′-OH acylation: Mechanisms determining nucleotide reactivity

Jash

Kool

2022

Chem. Commun.

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“…In relation to this, the Szostak lab recently demonstrated that the presence of a 3-amino group at the 3'-end of tetranucleotides enhances their ligation in the presence of an N-imidazole organocatalyst [90]. Secondly, it has been recently shown that coded peptide synthesis can proceed without tRNAs or ribosomes, specifically using single nucleotides charged with amino acids [91,92]. One can expect that charged trinucleotides may form more stable base-pairing interactions with corresponding templates compared to those observed with mononucleotides.…”

Section: A Testable Hypothesis For Primordial Rna Synthesis Coupled To Ribosome-free Translationmentioning

confidence: 99%

Genomes contain relics of a triplet code connecting the origins of primordial RNA synthesis to the origins of genetically coded protein synthesis

Siwo

2021

Preprint

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Life on earth relies on three types of information polymers-DNA, RNA and proteins. In all organisms and viruses, these molecules are synthesized by the copying of pre-existing templates. A triplet-based code known as the genetic code guides the synthesis of proteins by complex enzymatic machines that decode genetic information in RNA sequences. The origin of the genetic code is one of the most fundamental questions in biology. In this study, computational analysis of about 5,000 species level metagenomes using techniques for the analysis of human language suggests that the genomes of extant organisms contain relics of a distinct triplet code that potentially predates the genetic code. This code defines the relationship between adjacent triplets in DNA/RNA sequences, whereby these triplets predominantly differ by a single base. Furthermore, adjacent triplets encode amino acids that are thought to have emerged around the same period in the earth’s early history. The results suggest that the order of triplets in primordial RNA sequences was associated with the availability of specific amino acids, perhaps due to a coupling of a triplet-based primordial RNA synthesis mechanism to a primitive mechanism of peptide bond formation. Together, this coupling could have given rise to early nucleic acid sequences and a system for encoding amino acid sequences in RNA, i.e. the genetic code. Thus, the central role of triplets in biology potentially extends to the primordial world, contributing to both the origins of genomes and the origins of genetically coded protein synthesis.SignificanceOne of the most intriguing discoveries in biology is that the order of amino acids in each protein is determined by the order of nucleotides (commonly represented by the letters A, U, G, C) in a biological molecule known as RNA. The genetic code serves as a dictionary that maps each of the 64 triplets ‘words’ in RNA to the 20 amino acids, thereby specifying how information encoded in RNA is decoded into sequences of amino acids (i.e., proteins). The deciphering of the genetic code was one of the greatest discoveries of the 20th century (1968 Nobel Prize in Medicine and Physiology) and is central to modern molecular biology. Yet, how it came to be that the order of triplets in RNA encodes the sequence of the protein synthesized remains one of the most important enigmas of biology. Paradoxically, in all life forms proteins cannot be synthesized without RNA and RNA itself cannot also be synthesized without proteins, presenting a chicken and egg dilemma. By analyzing thousands of microbial genomes using approaches drawn from the field of natural language processing, this study finds that the order of triplets across genomes contains relics of an ancient triplet code, distinct from but closely connected to the genetic code. Unlike the genetic code which specifies the relationship between information in RNA and the sequence of proteins, this ancient code describes the relationship between adjacent triplets in extant genome sequences, whereby such triplets are often different from each other by a single letter. Triplets that are closely related by this ancient code encode amino acids that are thought to have emerged around the same period in the earth’s early history. In other words, a fossil record of the chronological order of appearance of amino acids on early earth appears written in genome sequences. This potentially demonstrates that the process by which RNA sequences were synthesized in the primordial world relied on triplets and was coupled to amino acids available at the time. Hence, the connections between primordial RNA synthesis and a primitive mechanism for linking amino acids to form peptides could have enabled one type of molecule (RNA) to code for the other (protein), facilitating the emergence of the genetic code.

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Single nucleotide translation without ribosomes

Cited by 40 publications

References 41 publications

A prebiotically plausible scenario of an RNA–peptide world

A prebiotically plausible scenario of an RNA–peptide world

Conjugation of RNA via 2′-OH acylation: Mechanisms determining nucleotide reactivity

Genomes contain relics of a triplet code connecting the origins of primordial RNA synthesis to the origins of genetically coded protein synthesis

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