Nonenzymatic copying of RNA templates containing all four letters is catalyzed by activated oligonucleotides

Though defining what makes something “alive” has proved challenging, one crucial feature of living things is the ability to copy genetic information and pass it on to the next generation. Nowadays, enzymes called polymerases copy genetic information encoded within the DNA of living cells. However, when life on Earth began approximately four billion years ago, polymerases had not evolved yet. This means that the genetic information of the first cells had to be copied some other way. The earliest life on Earth is unlikely to have used DNA to store its genetic information, and probably used a closely related molecule called RNA instead. Like DNA, RNA is made up of four smaller building blocks joined together to form long chains. The building blocks of RNA are commonly referred to using single letters: A, C, G and U. Previous studies have shown that it is possible to copy RNA without enzymes, but for only two of the four RNA letters, namely C and G. Prywes et al. wanted to know if it was possible to create a chemical system, without polymerases, in which all four RNA letters could be copied. The experiments showed that strings of RNA that were three letters long could catalyze RNA copying, just as long as they were chemically activated. That is to say, these short RNA strings allowed RNA to be copied without enzymes if they had a chemical group at one end that made them more reactive.Each short catalyst helped copy one of the four RNA letters, and adding several into one reaction meant that longer sequences containing all four RNA letters could be copied. Prywes et al. then used these short catalysts to copy an RNA molecule that itself acts a bit like an enzyme, and confirmed that a significant portion of this molecule could be copied without any polymerases. Further work is now needed to see if it is possible to copy other RNA sequences, and especially longer ones, without enzymes. Another challenge for the future would be to attempt to copy an RNA sequence multiple times without enzymes; a challenge that the earliest ancestors of cells on Earth must have overcome to pass their genetic information down through the generations.