• US scientists Victor Ambros and Gary Ruvkun won the 2024 Nobel Prize in Physiology or Medicine for the discovery of microRNA and its crucial role in how multicellular organisms grow and live.

• Ambros is a professor at the University of Massachusetts Medical School, while Ruvkun is a professor at Harvard Medical School and also affiliated with Massachusetts General Hospital in Boston.

• Their work helped explain how cells specialise and develop into different types, such as muscle and nerve cells, even though all the cells in an individual contain the same set of genes and instructions for growing and staying alive.

• The winners of the prize for physiology or medicine are selected by the Nobel Assembly of Sweden's Karolinska Institute medical university and receive a prize sum of 11 million Swedish crowns ($1.1 million).

• Created in the will of Swedish dynamite inventor and businessman Alfred Nobel, the prizes have been awarded for breakthroughs in science, literature and peace since 1901, while economics is a later addition.

What are microRNAs?

MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression and target essentially all coding transcripts.

• Function: miRNAs regulate gene expression by binding to mRNA molecules and inhibiting their translation into proteins. This process, known as post-transcriptional gene regulation, allows miRNAs to control the amount of protein that is produced by specific mRNAs. 

• Mechanism: miRNAs bind to complementary sequences within the mRNA, causing the mRNA to be degraded or preventing its translation, effectively silencing the gene it represents. 

Process of Protein Production:

• Transcription: DNA is transcribed into mRNA in the nucleus. 

• Translation: mRNA moves out of the nucleus to the ribosome, where it is translated into proteins with the help of transfer RNA (tRNA). 

• Regulation by miRNA: After transcription, miRNAs can bind to the mRNA and inhibit protein production, adding an extra layer of regulation to gene expression. 

Nobel-Winning Discovery:

• The discovery of miRNAs emerged from the research of Ambros and Ruvkun in the late 1980s, focusing on the roundworm Caenorhabditis elegans, a model organism for studying genetics and development. 

• The Discovery of lin-4: Ambros and Ruvkun worked with two mutant strains of C. elegans, lin-4 and lin-14, which exhibited developmental abnormalities due to issues with their genetic programming. 

• Ambros initially discovered that lin-4 suppressed the activity of lin-14 but was unsure of the mechanism.

• Through further research, Ambros identified that lin-4 produced a short RNA molecule that did not code for proteins. Ruvkun, in parallel, found that lin-4 did not block the production of lin-14 mRNA but instead inhibited protein production later in the gene expression process. 

• This finding led them to hypothesize that lin-4 acted as a microRNA that silenced lin-14 protein production.

• Their groundbreaking findings were published in 1993, but the concept of miRNA was initially met with skepticism, as it was thought to be specific to C. elegans. However, Ruvkun’s 2000 discovery of the let-7 microRNA, found across the animal kingdom, ignited further interest in miRNAs.

• Unregulated Regulation: The abnormal regulation of miRNAs can have serious implications for human health, including the development of cancers and genetic disorders. 

• Research Potential: While miRNAs have shown great promise in understanding gene regulation, much remains to be discovered. Understanding how miRNAs are involved in different physiological processes is the first step towards developing targeted therapies for various diseases. 

Applications of miRNA Research:

• Gene Regulation: miRNAs fine-tune gene expression, allowing for complex regulation of genes that lead to diverse cell types despite having similar genetic information.

• Cancer: Dysregulated miRNA activity can lead to abnormal protein production, contributing to diseases like cancer. Understanding miRNA regulation can potentially offer new pathways for cancer therapies.

• Genetic Disorders: Mutations in miRNA-related genes can cause diseases such as congenital hearing loss, eye disorders, and skeletal conditions.

• Drug Development: While there are currently no clear clinical applications, research into miRNAs may pave the way for therapeutic interventions targeting miRNA pathways.

(The author is a trainer for Civil Services aspirants.)