All cells of the same person contain the same chromosomes, but different types of cells such as muscle and nerve cells have different characteristics. What caused this difference? The answer lies in gene regulation, which allows each cell to only select instructions related to its own function, ensuring that different cells produce different proteins. The Karolinska Institute in Sweden announced on October 7th that the 2024 Nobel Prize in Physiology or Medicine will be awarded to American scientists Victor Ambrose and Gary Rufchan for their discovery of microRNA and its role in post transcriptional gene regulation. In the late 1980s, Ambrose and Rufchan studied a small worm less than 1 millimeter in length - Caenorhabditis elegans, and targeted its two mutant strains, "lin-4" and "lin-14". Ambrose discovered that the lin-4 gene appears to be a negative regulator of the lin-14 gene. However, the inhibitory mechanism is not clear. Until the end of his postdoctoral research, Ambrose unexpectedly discovered in his laboratory at Harvard University that the "mastermind" behind the suppression of the lin-14 gene by the lin-4 gene may be a type of ultra short RNA produced by lin-4. At the same time, Rufchan found that lin-4 did not affect the production of messenger RNA (mRNA) by the lin-14 gene, but rather inhibited the production of protein from mRNA. He also discovered a key fragment in the mRNA of lin-14, which serves as the "lever" for lin-4 to inhibit it. Ambrose and Rufchan reached a groundbreaking conclusion after their communication: the ultra short RNA in lin-4 complements the key fragment sequence of mRNA in lin-14, and ultra short RNA "shuts off" lin-14 by binding to mRNA, preventing it from producing proteins. This is the previously unknown gene regulatory mechanism based on microRNA. Previously, scientists believed that it was a special protein called a "transcription factor" that regulated genes by binding to specific regions of DNA and determining which mRNA to produce. From silence to great sensation, but when Ambrose and Rufchan published their findings in the journal Cell in 1993, they were met with the silence of the scientific community. Despite being an unprecedented discovery, the scientific community believes that this mechanism may be a characteristic of Caenorhabditis elegans, unrelated to humans and other more complex animals. It wasn't until 2000, when the Lufchan research team announced their discovery of another microRNA encoded by the let-7 gene, that silence became a huge sensation. Unlike lin-4, let-7 gene exists throughout the animal kingdom. This discovery sparked a "treasure hunt" in the scientific community, and in the following years, hundreds of different microRNAs were identified. Today, over a thousand types of microRNAs have been discovered in the human body. Without them, cells and tissues cannot develop normally, and their abnormalities and mutations may lead to serious diseases such as cancer. It can be said that the emergence of microRNAs has revealed a new dimension of gene regulation, which is crucial for all complex life forms. The process by which Ambrose and Rufchan discovered microRNAs is also full of legendary colors. (New Society)