All cells in the same person contain identical chromosomes, yet different cell types, such as muscle and nerve cells, exhibit vastly different characteristics. How do these differences arise? The latest answer lies in gene regulation, which allows different cells to produce distinct proteins.
The 2024 Nobel Prize in Physiology or Medicine was awarded to American scientists Victor Ambros and Gary Ruvkun in recognition of their discovery of microRNA (miRNA) and its role in post-transcriptional gene regulation.
A Small Worm Brings a Big Breakthrough
In the late 1980s, Ambros and Ruvkun were studying a tiny worm called Caenorhabditis elegans, measuring less than 1mm in length, focusing on two mutant strains, “lin-4” and “lin-14.” Coincidentally, Ambros had already discovered that the lin-4 gene appeared to negatively regulate the lin-14 gene, but the suppression mechanism was unclear.
It wasn’t until after finishing his postdoc that Ambros made an unexpected discovery in his lab at Harvard. He found that the lin-4 gene produced an unusually short RNA (which we now know as microRNA) that was the “mastermind” behind the suppression of lin-14. Meanwhile, Ruvkun discovered that lin-4 did not prevent the production of lin-14 mRNA but instead inhibited the mRNA from producing proteins. He also found that a key segment in lin-14’s mRNA served as the binding site for lin-4’s suppression.
After exchanging their findings, the two scientists arrived at a groundbreaking conclusion: a short RNA from lin-4 was complementary to a crucial sequence in lin-14 mRNA. By binding to this sequence, the short RNA effectively “turned off” lin-14, preventing protein production. This revealed a previously unknown gene regulation mechanism based on microRNA.
Before this discovery, scientists believed that gene regulation was primarily controlled by special proteins called “transcription factors” that determined which mRNA was produced by binding to specific regions of DNA.
From Silence to Scientific Uproar
However, when Ambros and Ruvkun published their findings in Cell in 1993, the response from the scientific community was muted. Despite the unprecedented nature of their discovery, many scientists believed that this mechanism might be unique to C. elegans and irrelevant to humans or more complex animals.
That silence continued until 2000, when Ruvkun’s research group announced another groundbreaking discovery: the identification of a different microRNA encoded by the let-7 gene, which, unlike lin-4, was present throughout the animal kingdom. This sparked a scientific “gold rush,” with hundreds of different microRNAs identified in the following years.
Today, we know that humans have over a thousand different types of microRNAs, without which cells and tissues would fail to develop properly. Mutations or abnormalities in these microRNAs can lead to serious diseases such as cancer. The discovery of microRNA opened up an entirely new dimension in gene regulation, one crucial for all complex life forms. The journey that Ambros and Ruvkun undertook to uncover microRNA is as legendary as the discovery itself.
A Tribute to Scientists Who Endure “Loneliness”
It has been 30 years since the discovery of the first microRNA. It’s hard to imagine that the now-flourishing field of microRNA research was once marginalized and even “selectively ignored.” For a long time, Victor Ambros and Gary Ruvkun were solitary pioneers in their research, with few competitors in the field.
The path of scientific exploration is often described as a lonely journey, known only to those who walk it. Scientists must face long periods of independent research, countless experimental failures, and even skepticism from peers or prominent figures. However, this loneliness is not always negative—it provides space for deep thought and innovation. In such an environment, scientists can pursue unanswered questions without distractions. This persistence allows the boundaries of human knowledge to expand continuously, and this spirit inspires every researcher who tirelessly strives for discovery.
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