Micro finding honoured
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Two scientists who uncovered life's hidden instructions have a Nobel Prize.
Victor Ambros and Gary Ruvkun have been awarded the 2024 Nobel Prize in Physiology or Medicine for their pioneering work on the discovery of microRNA, a previously unknown molecule that plays a vital role in regulating gene expression.
The Nobel Assembly at Karolinska Institutet has honoured the two scientists for uncovering a key principle of gene regulation, a mechanism that ensures that genes in various cell types are turned on or off at the right times.
This discovery has profound implications for understanding how organisms develop, function, and adapt.
MicroRNAs are tiny RNA molecules that regulate gene activity after transcription - the stage where DNA is copied into messenger RNA (mRNA).
These molecules do not code for proteins but instead bind to mRNA to either block protein production or promote the degradation of the mRNA itself.
This form of regulation, known as post-transcriptional regulation, fine-tunes gene expression in a way that allows specific cell types - like muscle, nerve, or intestinal cells - to perform their specialised functions, even though they all share the same DNA.
Ambros and Ruvkun’s research dates back to the late 1980s when they were studying a small roundworm, Caenorhabditis elegans, in the lab of Robert Horvitz, a 2002 Nobel laureate.
Their research focused on mutant strains of worms that exhibited developmental timing defects, leading to the discovery of lin-4 and lin-14 genes, which played a role in this process.
The breakthrough came when they identified that the lin-4 gene produced a short, non-coding RNA molecule - microRNA - which regulated the activity of the lin-14 gene by binding to its mRNA and blocking protein synthesis.
This revelation, published in 1993, was initially met with silence from the scientific community, as many believed that this mechanism of gene regulation was unique to worms and unlikely to be relevant to humans.
However, this perception dramatically shifted in 2000, when Ruvkun’s lab identified a second microRNA, let-7, which was found to be highly conserved across a wide range of animal species, including humans.
This discovery ignited widespread interest and led to the identification of hundreds of microRNAs in various organisms.
Today, scientists know that the human genome contains more than a thousand different microRNA genes, each of which plays a crucial role in regulating networks of protein-coding genes.
Since the mid-20th century, scientists had believed they understood the main mechanisms behind this flow, particularly the role of transcription factors - special proteins that control which genes are expressed by binding to specific DNA regions.
However, Ambros and Ruvkun’s discovery of microRNAs introduced an entirely new layer of regulation that occurs after the transcription phase, adding an unexpected complexity to the system.
Research has since shown that microRNAs are vital for the proper development and function of multicellular organisms.
These molecules help ensure that gene expression is continually fine-tuned, allowing cells to adapt to changing conditions both within the body and in response to the external environment.
If gene regulation via microRNAs goes awry, it can contribute to various diseases, including cancer, autoimmune disorders, and developmental abnormalities.
For example, mutations in genes coding for microRNAs or the proteins involved in their production have been linked to conditions such as congenital hearing loss, eye disorders, and even certain cancers, such as those associated with DICER1 syndrome.
Ambros and Ruvkun’s discovery has also opened doors to understanding how genetic networks are coordinated.
A single microRNA can regulate the expression of multiple genes, and a single gene can be controlled by various microRNAs.
This intricate system allows cells to maintain balance in gene activity, coordinating their functions for the overall development and homeostasis of the organism.
The unexpected discovery of microRNA by Ambros and Ruvkun has shown that these small molecules have been at work for hundreds of millions of years, playing a crucial role in the evolution of complex life forms.
Their discovery not only reshaped the world’s understanding of gene regulation but also opened up new possibilities for medical research, particularly in the field of genetic disorders and potential therapeutic applications.
More details of their discoveries are accessible in PDF form, here.