A new RNA: Nobel prize awarded to Cambridge scientists for discovery of microRNA

DNA and RNA are often hailed as the “code of life.” This isn’t far from the truth. DNA and RNA are nucleic acids, made up of a sequence of chemical components called nucleotides. The order of these nucleotides encodes genetic information in the form of genes, which are transcribed from DNA into RNA before directing protein formation during a process known as translation. 

On October 7, the 2024 Nobel Prize in Medicine was presented to Drs. Victor Ambros and Gary Ruvkun in Cambridge, Massachusetts for their discovery of microRNA. MicroRNA is a revolutionary new member of the RNA community, a single–stranded analog of DNA essential to the growth and development of all life. This newfound biomolecule plays an important role in gene regulation, specifically in determining whether or not DNA transcripts are translated into biologically active proteins. 

Drs. Ruvkun and Ambros first published their Nobel–winning findings on microRNA in 1993. Aiming to understand the timeline of cellular dynamics during development, the laureates had been studying two strains of Caenorhabditis elegans with mutations in the Lin–4 and Lin–14 genes. It was already known that the Lin–4 gene negatively regulated the activity of Lin–14 thanks to prior work done by Ambros, but the underlying explanation was uncertain. The two scientists began their collaboration to identify this mechanism, and the Nobel–winning discovery came soon after. They found that Lin–4 was translated into a short, non–coding RNA molecule that could bind to the mRNA transcript of Lin–14, preventing it from translation into a protein product. This short molecule would come to be known as microRNA. 

“MicroRNA is a revolutionary new member of the RNA community, a single–stranded analog of DNA essential to the growth and development of all life.”

Expanding upon this discovery, Ruvkun and Ambros then demonstrated that microRNAs are integral in late–stage gene regulation. By binding mRNA, they can physically block protein synthesis or cause mRNA to be degraded before it can be translated. The true significance of this discovery, for a while, fell flat until it was later corroborated in separate labs among more complex multicellular organisms like zebrafish, mice, and humans. The genetic origins and functional mechanisms of microRNA were discovered to be conserved across a variety of complex multicellular species, suddenly adding greater depth and significance to the realm of genetics.

Gene regulation is an increasingly compelling topic of interest in the scientific community. Over half of the human genome is estimated to code for regulatory elements, while less than 2% of the genome consists of actual genes. This abundance of genetic regulatory elements emphasizes the biological importance of the process. This importance is further qualified by the fact that regulatory dysfunction is a known contributor to the pathophysiology of many medical disorders like Huntington’s disease.

There are many methods of gene regulation, many involving noncoding RNA molecules. Named for its abnormally short sequence of only 22 nucleotides, microRNA is single–stranded noncoding RNA, and it is particularly striking because it is an endogenous, post-transcriptional regulator. Other known noncoding RNAs are either exogenously derived (like siRNAs, from external genomes such as viruses) or regulate the genome in an entirely different mechanism (like lncRNAs, that alter chromatin structure).

The conferment of this year’s Nobel Prize for the discovery of microRNA is well–deserved. The strong conservation of microRNA across multicellular organisms and endogenous origins indicates that there is a far greater depth to self–regulation of gene expression than previously thought. Further, microRNA presents significant medical potential for its role in disease pathology, possibly serving as a tool for defining and distinguishing disease states. MicroRNA only further exemplifies the immense complexity and evolutionary achievements of modern organisms, and is just another facet of the inseparable nature of RNA and the very fact of life.