Pre-Discovery
We all know that cells make transcripts from their genome to build their proteins. However, before the discovery of messenger RNA (mRNA), the mechanism by which genetic information was transferred from DNA to proteins was unclear. Scientists knew that DNA carried genetic instructions and that proteins performed cellular functions, but the intermediary between the two was unknown. The dominant theory suggested that DNA directly guided protein synthesis, but this view was challenged as research progressed.
By the early 1950s, it was established that DNA resided in the nucleus, while protein synthesis occurred in the cytoplasm. This raised a fundamental question: how did genetic information travel from the nucleus to the ribosomes? Scientists suspected an intermediary molecule, but its nature remained elusive. The discovery of transfer RNA (tRNA) and ribosomal RNA (rRNA) hinted at the complexity of the process, but a dedicated carrier of genetic instructions had not yet been identified.
The Story of Discovery
The concept of messenger RNA emerged in the early 1960s when two groups independently proposed that a temporary RNA molecule carried genetic information from DNA to ribosomes. In 1961, François Jacob and Sydney Brenner conducted experiments with bacteriophages and bacteria, demonstrating that a short-lived RNA molecule, distinct from rRNA, directed protein synthesis. They named this molecule “messenger RNA”. The other group was led by James D. Watson (who proposed the double helix structure of DNA) and François Gros, working on the mechanism of gene reading.
One interesting and foundational experiment was François Gros’s use of an RNA synthesis inhibitor, which led to the pause of protein synthesis. The interesting point was that François Gros and François Jacob met each other in the USA before the discovery of mRNA and discussed their research, although not focusing on mRNA itself.
Further studies confirmed that mRNA served as the missing link between DNA and protein synthesis.
It was transcribed from DNA in the nucleus and transported to ribosomes, where it provided the instructions for assembling proteins. This discovery was pivotal, leading to the central dogma of molecular biology: DNA → RNA → Protein.
Following the discovery
The discovery of mRNA revolutionized molecular biology by explaining how genetic information was expressed within cells. Researchers soon uncovered the elements of mRNA and the mechanisms of transcription and translation, further deepening our understanding of gene regulation and expression.
Decades later, mRNA technology became the foundation for groundbreaking medical advances. In the 1990s and early 2000s, Katalin Karikó and Drew Weissman explored synthetic mRNA modifications, leading to the development of mRNA-based vaccines. This technology gained global recognition during the COVID-19 pandemic, as mRNA vaccines by Pfizer-BioNTech and Moderna played a critical role in controlling the virus.
Takeaways
1. Questioning Assumptions: Before mRNA’s discovery, scientists assumed DNA directly influenced protein synthesis. Challenging this assumption led to a fundamental shift in molecular biology.
2. Believing in Your Work: Early work on mRNA faced skepticism, and it took decades for the technology to be recognized. Katalin Karikó and Drew Weissman struggled for years before their research laid the foundation for mRNA vaccines.
3. Impact of Basic Research: The study of mRNA began as a purely scientific endeavor with no immediate application, yet it became the foundation of life-saving vaccines. Fundamental discoveries can be adapted to meet urgent global challenges.
4. Idea Sharing: The discovery of mRNA was the result of international collaboration and discussions between researchers in different labs from Institut Pasteur to Harvard University to Caltech. Engaging with the scientific community and exchanging ideas can lead to transformative insights.
References
1. Cobb M. (2015). Who discovered messenger RNA?. Current biology: CB, 25(13), R526–R532.
2. Discovery of messenger RNA in 1961, Institut Pasteur
3. GROS, F., HIATT, H., GILBERT, W., KURLAND, C. G., RISEBROUGH, R. W., & WATSON, J. D. (1961). Unstable ribonucleic acid revealed by pulse labelling of Escherichia coli. Nature, 190, 581–585.
4. Brenner, S., Jacob, F., & Meselson, M. (1961). An Unstable Intermediate Carrying Information from Genes to Ribosomes for Protein Synthesis. Nature, 190, 576–581.
5. Karikó, K., & Weissman, D. (2005). Suppression of RNA Recognition by Toll-like Receptors. Immunity, 23(2), 165–175.