Victor Ambros and Gary Ruvkun have been awarded the Nobel Prize for their groundbreaking work on “the discovery of microRNA and its role in post-transcriptional gene regulation.” Here’s a breakdown of what this means and why it is significant.
This year, the Nobel Prize in Medicine has been awarded to Victor Ambros and Gary Ruvkun. According to the Nobel Prize website, the American scientists were recognized for “the discovery of microRNA and its role in post-transcriptional gene regulation.”
So, what is microRNA, and why is it important? What have Ambros and Ruvkun achieved, and how might their work be applied in the future? Let’s explore.
What is microRNA?
MicroRNA is a small, non-coding RNA molecule that plays a crucial role in gene expression regulation.
MicroRNA molecules play a crucial role in helping cells regulate their protein production. The proteins produced by cells are essential for nearly all biological processes in living organisms. For example, in the human body, hemoglobin carries oxygen, while insulin helps the body absorb glucose from the bloodstream. Therefore, anything that affects protein production can have significant implications for human health.
MicroRNA functions by binding to another type of molecule known as messenger RNA (mRNA). As noted in an article from Ohio State University, “microRNA controls gene expression primarily by interacting with messenger RNA (mRNA) in the cell cytoplasm. Instead of being quickly translated into a protein, the targeted mRNA can either be destroyed and its components recycled or preserved for later translation.”
In the 1980s, Victor Ambros and Gary Ruvkun were postdoctoral fellows in Robert Horvitz’s laboratory, who later won the Nobel Prize in 2002. During their research, they focused on a tiny roundworm known as C. elegans, which shares certain cell types with more complex animals.
According to the Nobel Prize website, “They examined two mutant strains of worms, lin-4 and lin-14, that exhibited issues with the timing of genetic program activation during development.”
In earlier research, Ambros had demonstrated that the lin-4 gene suppressed the lin-14 gene, but the mechanism behind this effect remained unclear. During his investigations, Ambros discovered that the lin-4 gene produced a uniquely short RNA molecule that inhibited lin-14. This short RNA molecule was identified as microRNA.
At the same time, Ruvkun focused on studying lin-14. During this period, it was widely believed that to regulate a gene, the production of its mRNA had to be targeted. However, Ruvkun discovered that lin-4 did not inhibit the production of mRNA from lin-14. Instead, the regulation occurred at a later stage in gene expression by shutting down protein production.
His experiments revealed a specific segment in lin-14 mRNA that was crucial for its inhibition by lin-4. By comparing their findings, the two researchers made a significant breakthrough. They found that the short lin-4 sequence matched complementary sequences within this critical segment of lin-14 mRNA. Further experiments showed that lin-4 microRNA effectively turned off lin-14 by binding to these complementary sequences, preventing the production of lin-14 protein.
Although their results were published in 1993, they initially went unnoticed, as it was believed that this type of gene regulation was exclusive to the roundworm C. elegans. However, subsequent research has demonstrated that microRNA is present in all multicellular organisms, including humans.
Why is their research significant?
When gene regulation goes awry, it can lead to serious diseases such as cancer, diabetes, and autoimmune disorders. This understanding has made the regulation of gene activity a crucial focus for researchers over many decades. The role of microRNA in gene regulation, first uncovered by Ambros and Ruvkun, has been active for hundreds of millions of years. Genetic studies have shown that cells and tissues cannot develop normally without microRNAs.
Abnormal regulation by microRNA can contribute to the development of cancer, and mutations in the genes that code for microRNAs have been associated with various human conditions. These include congenital hearing loss as well as disorders affecting the eyes and skeletal system, highlighting the significant impact that microRNA has on health and development.