A reverse transcriptase ribozyme
Biswajit Samanta Gerald F Joyce Is a corresponding author
The Salk Institute, California
SHORT REPORT Sep 26, 2017
Reverse transcriptase activity of the 24–3 ribozyme.
Abstract
A highly evolved RNA polymerase ribozyme was found to also be capable of functioning as a reverse transcriptase, an activity that has never been demonstrated before for RNA. This activity is thought to have been crucial for the transition from RNA to DNA genomes during the early history of life on Earth, when it similarly could have arisen as a secondary function of an RNA-dependent RNA polymerase. The reverse transcriptase ribozyme can incorporate all four dNTPs and can generate products containing up to 32 deoxynucleotides. It is likely that this activity could be improved through evolution, ultimately enabling the synthesis of complete DNA genomes. DNA is much more stable compared to RNA and thus provides a larger and more secure repository for genetic information.
eLife digest
All known living things share the same genetic machinery, traditionally called the central dogma. According to this dogma, genes in DNA produce messages made from a similar molecule called RNA. These RNA messengers provide the instructions to make proteins, which then form structures and act as molecular machines inside cells. This process is found in all modern living things, but early life must have been much simpler.
Many biologists believe that the earliest life only used RNA, which can both store information like DNA and perform tasks like a protein. Life evolved from this so-called ‘RNA world’ because DNA provides a more reliable long-term store of information, whilst proteins are more versatile and able to perform more tasks. This key step in evolution allowed life to move beyond basic chemistry and develop the size, complexity and diversity we see today. Yet, how this transition happened is not well understood. In particular, many believe an RNA molecule must have evolved the ability to make DNA from an RNA template, allowing early life to build the first genetic material made from DNA. This molecule would be referred to as a reverse transcriptase ribozyme.
Modern living things do not contain such a molecule. Yet based on their previous work using RNA molecules to make copies of other RNAs, Samanta and Joyce attempted to develop an artificial reverse transcriptase ribozyme. The goal was to show that these ribozymes can be made and could theoretically have evolved naturally. The molecule Samanta and Joyce created was able to reliably produce short sections of DNA, with rare errors. This ribozyme is slower and makes more mistakes than molecular systems in modern biology, but it proves that reverse transcriptase ribozymes are possible.
Using a process called test-tube evolution, which uses the same concepts as natural evolution to improve the qualities of biological molecules, Samanta and Joyce now plan to improve their ribozyme. The aim is to confirm that a reverse transcriptase ribozyme could have been a transformative early step in evolution of life on Earth that led to the first DNA genomes. This will be a critical addition to scientists’ understanding of how life became more complex and how the first cells formed.
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