How life could have appeared in an “RNA world”

It’s the ultimate chicken and egg riddle. Life does not function without tiny molecular machines called ribosomes, whose job it is to translate genes into proteins. But the ribosomes themselves are made up of proteins. So how was the first life born?

Researchers may have taken the first step toward solving this mystery. They showed that RNA molecules can grow short proteins called peptides on their own – no ribosomes are required. Moreover, this chemistry works under conditions likely present on early Earth.

“It’s an important step forward,” says Claudia Bonfio, an original chemist at the University of Strasbourg who did not take part in the work. The study, she says, offers scientists a new way to think about how peptides were constructed.

Researchers studying the origin of life have long considered RNA to be the central player because it can both carry genetic information and catalyze necessary chemical reactions. It was probably present on our planet before life evolved. But to give rise to modern life, RNA would have had to somehow “learn” to make proteins, and eventually ribosomes. “At the moment, the ribosome just falls from the sky,” says Thomas Carell, a chemist at the Ludwig Maximilian University in Munich.

A clue to this conundrum came from previous lab work. In 2018, Carell and his colleagues were trying to figure out how the four “canonical” bases of RNA could have formed from simpler molecules. In modern cells, these RNA bases – guanine, uracil, adenine and cytosine – make up the genetic letters of messenger RNA (mRNA) that ribosomes read and translate into proteins. However, other “non-canonical” RNA bases are also ubiquitous in modern cells, fulfilling various roles. These include stabilizing the bond between canonical RNAs and “transfer RNAs” that help ribosomes convert the genetic code from mRNA into proteins.

Carell and his colleagues noticed that some of these non-canonical RNAs could have been synthesized from single molecules on early Earth. They and others went on to show that certain non-canonical bases could bind to amino acids, the building blocks of proteins, raising the possibility that they could also bind them together into peptides.

Now Carell’s team reports that a non-canonical RNA base pair can do just that. They started with pairs of RNA strands, each made up of chains of RNA bases linked together in a chain. These pairs of strands were complementary, allowing them to recognize and bind to each other. At one end of the first strand – called the “donor” strand – they included a non-canonical RNA base, called at6A, which is able to bind to an amino acid. At the end of the second strand of RNA, called the “acceptor” strand, they added another non-canonical RNA base, called mnm5U.

Carell’s team found that when complementary donor and acceptor RNA strands bind, the mnm5U grabs the amino acid on the t6A. With the addition of a little heat, t6To let go and switch his amino acid to mnm5U, and complementary strands dissociate and separate.

But the process could repeat itself. A second donor strand carrying another amino acid could then bind to the acceptor strand, and pass on its amino acid, which was bound to the first. The process could create peptide chains up to 15 amino acids long, the team reports today in Nature.

Carell and his colleagues also found that when complementary RNA strands containing non-canonical RNA base pairs bind together, the amino acids they initially share strengthen the binding of the two RNA strands. The result, says Bonfio, is that on early Earth, the formation of peptides and RNA may have been synergistic: RNAs may have helped form peptides, and peptides may have helped stabilize and form RNAs still longer.

She and Carell say this synergy could have produced a huge chemical diversity of RNA, peptides and combinations of the two that could then have given rise to the complex chemistry necessary for life, all without the need for ribosomes.

Carell acknowledges that the work is just a “first stepping stone”. Researchers have yet to demonstrate how strands of RNA – containing canonical or other bases – could have selected for specific chains of amino acids needed by real proteins. But with a stepping stone in place, origin-of-life researchers now have an idea of ​​where to go.

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