Victor Ambros and Gary Ruvkun were jointly awarded the 2024 Nobel Prize in physiology or medicine for discovering microRNA and its role in post-transcriptional gene regulation, as announced in Sweden by the Nobel Assembly at the Karolinska Institute Oct. 7.
The pair first worked together as postdoctoral fellows in the lab of Robert Horvitz at the Massachusetts Institute of Technology in the late 1980s. Currently, Ambros works as a professor at the University of Massachusetts Chan Medical School while Ruvkun is a professor of genetics at Harvard Medical School.
The importance of this discovery can be traced to how cells produce proteins, which are complex molecules that do much of the work in cells. Proteins are made through the consecutive processes of transcription and translation. During transcription, messenger RNA, or mRNA, copies genetic information from DNA, which is then converted into proteins during translation.
MicroRNA, or miRNA, are small, noncoding RNA molecules, meaning they do not code for proteins. Instead, miRNA prevent the translation of mRNA into proteins by binding to complementary mRNA sequences. The guide strand of miRNA, which identifies and pairs with specific RNA bases, facilitates this complementary binding process. Through this mechanism, miRNA can inhibit protein formation, thereby regulating various cellular and bodily processes.
Sinu John, adjunct associate professor of biochemistry at Georgetown University Medical Center and staff scientist at the National Institute of Allergy and Infectious Diseases, said miRNA are crucial to the understanding and treatment of diseases.
“Thousands of individual microRNAs regulate more than 60% of the total protein-coding genes in humans, and this has serious implications for the mechanism of disease pathogenesis and in developing novel biotechnology applications,” John told The Hoya.
John’s recent unpublished research showcases the potential impacts of miRNA regulation on immune responses, specifically inflammation.
“We have found that some miRNAs regulate inflammation in response to viral and bacterial infection. Consequently, without these miRNA genes expressed, there are serious negative impacts on immune responses,” John said. “Through functional genomic studies, we analyzed miRNAs and developed a better understanding of their function in immune regulation.”
John said the recent Nobel Prize highlighted miRNA’s importance and gave it recognition in mainstream science.
“Identifying the role of individual miRNA is vital for developing therapeutic strategies for many human diseases and the development of novel tools in biotechnology,” John said. “The Nobel Prize was given due to the increased recognition of miRNA in the field of epigenetic regulation, and it indicates the importance of this discovery to the public sphere, encouraging more exploration of this discovery.”
Jan LaRocque, professor of genetics in the Georgetown University School of Health, said miRNA has had a significant impact on biotechnological applications.
“One way in which miRNAs transformed biotechnology was when we harnessed the power of these molecules and applied them to small interfering RNA technology (siRNAs),” LaRocque said. “Utilizing the same mechanisms to silence gene expression, siRNA technology has changed how we are able to determine the role of different proteins in a plethora of biological contexts.”
Dr. Jeffrey Toretsky, chief of pediatric hematology and oncology at MedStar Georgetown University Hospital, also said miRNA are useful for experiments. By inhibiting the creation of specific proteins, miRNA can elucidate the true function of those proteins.
“As a laboratory research tool it’s been brilliant because it allows us to regulate gene expression and how cells work. By turning something off we see how it actually works,” Toretsky told The Hoya.
Toretsky said the Nobel Prize underscores the importance of basic scientific research, or research for the sake of knowledge rather than to answer a particular question.
“They just thought it was cool that cells used this mechanism to regulate their own transcripts, their own protein production,” Toretsky said. “The fact that it’s now recognized at the level of a Nobel Prize for these initial ideas underscores how important basic research is in learning about things that we don’t yet know are going to be important.”
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