A new paper: RNA-directed peptide synthesis without ribosomes

One of the most peculiar aspects of life is the relationship between two biopolymers…polynucleotides (incl. RNA and DNA) and polypeptides (incl. proteins). Structurally, they are polymers each with variable monomers that are able to link in any order, but chemically speaking, they have little in common. Yet, life makes peptides wherein the sequence of the monomers (amino acids) are determined by the sequence of the monomers in the polynucleotides. Since there are 20+ variable monomers in the former and only 4 variable monomers in the latter, this necessitates that each amino acid in the polypeptide chain is determined by triplet(s) of 3 nucleotides. This process of RNA-directed polypeptide synthesis is more often referred to as ‘translation’, and the mapping between the nucleotide triplets (codons) and amino acids as the ‘genetic code’, since we like to use metaphors in biology.

This is what the system actually “looks like” (not really, this is just a very simplified cartoon of course)


The mRNA (messenger RNA) contains the triplets that determines the sequence of amino acids in the polypeptide, but the larger structure called the ribosome is responsible for the chemical synthesis of the polypeptide. The amino acids are carried by tRNA (transfer RNA) to the ribosome. Each tRNA has a unique “anticodon” sequence that can bind to a unique codon on the mRNA. Aminoacyl tRNA synthases are responsible for charging each tRNA with the correct amino acid (which is where the genetic code is).

Interesting side note: The mRNA and tRNA are all made of RNA, but the ribosome too is made of RNA. Although the ribosome is also composed of protein, the protein is not necessary because the part that does synthetic chemistry is RNA based.

All of this begs the question…how could this have come about? Let’s not start at the beginning of abiogenesis all together, otherwise this thread would become a book. Let’s focus on this system alone and ask if this could have a simpler antecedent. There actually could. This is where the recent paper come in.

What they did was charging single RNA nucleotides with an amino acid, and also amino acids linked to the 5’ end of an RNA nucleotide. The base pairing between the RNA nucleotides determined which peptide was formed preferentially. So we have very simple system of translation that can make short chain of peptides with a degree of fidelity that adheres to a weak genetic code…but without a complex ribosome.

As alluded before, this alone certainly doesn’t answer all the questions of abiogenesis. This doesn’t answer every question about all aspects of translation specifically. What it does show is that

a single-nucleotide-based form of translation exists that requires no more than oligoribonucleotides and anchored amino acids.

https://www.nature.com/articles/s41557-021-00749-4

https://www.nature.com/articles/s41557-021-00760-9

Unfortunately, the paper and news&views article are behind a paywall. Sorry.

9 Likes

Incredibly fascinating. Particularly (given what little I can glean from the abstract) that the system seems to already consist of extremely simplified, plausible precursors of both tRNA and mRNA. It seems to basically follow biochemically that a ribozyme, which would be a simpler ancestor of the ribosome, could evolve to assist the template-guided polymerization of peptides.

Given the recent demonstration that a fully protein-free(pure RNA) and extremely simplified ribosomal core can catalyze multiple sequential peptide bonds it seems scientists are making considerable experimental progress on the evolution of the translation system.

6 Likes

Thank you for a summary so clear and simpler that even a humble statistician can understand it. :slight_smile:

1 Like

This topic was automatically closed 7 days after the last reply. New replies are no longer allowed.