Why is it in the news?

• On October 7, 2024, the Nobel Prize in Physiology or Medicine was awarded to Victor Ambros and Gary Ruvkun for their groundbreaking discovery of microRNA and its critical role in post-transcriptional gene regulation.
• Both are esteemed American biologists, with Ambros currently affiliated with the Programme in Molecular Medicine at the University of Massachusetts, and Ruvkun serving as a professor of genetics at Harvard Medical School.
• Their collaborative work began in the late 1980s while they were postdoctoral fellows in H. Robert Horvitz’s laboratory, who himself received the Nobel Prize in 2002 for his work in developmental biology.

Research Overview

• MicroRNAs (miRNAs) are small, non-coding RNA molecules, typically consisting of 19-24 nucleotides. They are integral to regulating how much messenger RNA (mRNA) is translated into proteins.
• The process of protein synthesis involves two main steps: transcription, where DNA is copied into mRNA, and translation, where mRNA is used to synthesize proteins.
• MicroRNAs regulate this process by binding to specific mRNAs and silencing them, effectively controlling protein production after transcription.
• Ambros and Ruvkun’s research focused on the model organism Caenorhabditis elegans, a small roundworm with distinct cell types. They investigated mutant strains, lin-4 and lin-14, which exhibited developmental abnormalities.
• Ambros initially demonstrated that lin-4 inhibited lin-14’s activity but could not determine how this suppression occurred. Later, Ruvkun discovered that lin-4 did not prevent the production of lin-14 mRNA but instead inhibited its protein synthesis.
• Their collaborative efforts revealed that the short lin-4 sequence could pair with specific segments of lin-14 mRNA, leading to the conclusion that lin-4 microRNA blocks the production of lin-14 protein.
• The pivotal findings were published in 1993, though initially met with skepticism, as many scientists considered the behaviour specific to elegans. Interest surged in 2000 when Ruvkun’s group identified another microRNA, let-7, which is found across the animal kingdom.
• This opened the door to understanding that microRNA regulation is a universal phenomenon in multicellular organisms, with over a thousand genes for various microRNAs identified in humans.
• MicroRNAs can regulate the expression of multiple genes, allowing for the fine-tuning of cellular functions despite similar genetic backgrounds. However, dysregulation of microRNAs can lead to diseases, including cancer and genetic disorders.
• While current applications of microRNAs remain limited, understanding their function is a crucial first step for future research in this area, as highlighted by Gunilla Karlsson-Hedestam, chairperson of the Nobel Committee for Physiology or Medicine 2024.