Soon after co-discovering the double helix, Francis Crick coined the term “central dogma of biology” to illustrate the flow of genetic information within biological systems. The basic idea is simple: DNA is the king of the cell, proteins are its major workforce, and RNA is a sort of a middle manager. He later admitted that dogma was a poor word choice for a rule that has exceptions. Indeed, he became one of the proponents of the RNA world hypothesis, where RNA is the primordial substance in the evolutionary history of life on Earth. We can only guess what the great British scientist might say about RNA taking the stage today.
Think of the mRNA vaccines against Covid-19, but also of guide RNAs in CRISPR/Cas9 genome editing. The pegRNA used in prime editing is twice as important because its job is to both identify the target site and provide the new genetic information, turning the central dogma on its head. Reverse transcription is well-known in retroviruses but, surprisingly enough, even a few mammalian enzymes can transcribe RNA into DNA (see the latest finding in Science Advances).
In short, RNA is cool today, but it was once a neglected subject. Before co-inventing CRISPR, Jennifer Doudna was busy doing RNA chemistry, working to figure out the 3D structure of self-splicing RNA. According to her biographer Walter Isaacson, she follows the same guiding principles now as then. “Never do something that a thousand other people are doing” and “Ask big questions”. What’s next?