It’s the ultimate chicken and egg puzzle. Life doesn’t work without tiny molecular machines called ribosomes, whose job it is to translate genes into proteins. But ribosomes themselves are made of proteins. So how did the first life come about?
Researchers may have taken the first step in solving this mystery. They have shown that RNA molecules can grow short proteins called peptides all by themselves – no ribosome required. Furthermore, this chemistry works under conditions likely to exist on early Earth.
“This is an important advance,” says Claudia Bonfio, an Origin of Life chemist at the University of Strasbourg, who was not involved in the work. The study, she says, offers scientists a new way of thinking about how peptides were constructed.
Researchers studying the origin of life have long considered RNA to be a key player because it can both carry genetic information and catalyze necessary chemical reactions. It was probably present on our planet before life evolved. But in order for modern life to emerge, RNA would have had to somehow “learn” how to make proteins and eventually ribosomes. “Right now, the ribosome is just falling out of the sky,” says Thomas Carell, a chemist at the Ludwig Maximilian University of Munich.
A clue to this puzzle came from earlier laboratory work. In 2018, Carell and his colleagues were trying to understand how RNA’s four “canonical” bases might have formed from simpler molecules. In modern cells, these RNA bases — guanine, uracil, adenine, and cytosine — make up the genetic letters in messenger RNA (mRNA) that the ribosomes read and translate into proteins. But other “non-canonical” RNA bases are also ubiquitous in modern cells and fulfill a variety of functions. This includes stabilizing the bond between canonical RNAs and the “transfer RNAs” that help the ribosomes convert the mRNA’s genetic code into proteins.
Carell and his colleagues found that some of these non-canonical RNAs could have been synthesized from simple molecules on early Earth. She and others went on to show that some noncanonical bases can bind to amino acids, the building blocks of proteins, raising the possibility that they could also join these into peptides.
Now, Carell’s team reports that a pair of noncanonical RNA bases 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 contained a non-canonical RNA base called at6A that can bind an amino acid. At the end of the second strand of RNA – the so-called “acceptor” strand – they added another non-canonical RNA base called mnm5u
Carell’s team found that when the complementary donor and acceptor RNA strands bind to each other, the mnm5U grabbed the amino acid on the t6A. With the addition of just a little bit of heat, t6A released and gave his amino acid to mnm5U, and the complementary strands dissociated and drifted apart.
But the process could repeat itself. A second donor strand, bearing a different amino acid, could then bind to the acceptor strand and pass on the amino acid linked to the first. The process could generate peptide chains up to 15 amino acids in length, the team reports today in Nature.
Carell and his colleagues also found that when complementary RNA strands containing pairs of noncanonical RNA bases bind to each other, amino acids they originally share strengthen the binding of the two RNA strands. The result, Bonfio says, is that on early Earth, the formation of peptides and RNAs may have been synergistic: RNAs may have helped form peptides, and peptides may have helped stabilize and form longer and longer RNAs.
She and Carell say this synergy could have produced an enormous chemical diversity of RNAs, peptides, and combinations of the two, which could then have led to the complex chemistry needed for life — all without the need for ribosomes.
Carell admits the work is just “a first stepping stone.” Researchers have yet to show how strands of RNA — containing canonical bases or others — could have selected for specific chains of amino acids needed for actual proteins. But with a springboard, researchers now have an idea of where to look next.