The 2024 Nobel Prize in Physiology or Medicine celebrates a landmark breakthrough in molecular biology: the discovery of microRNAs by Victor Ambros and Gary Ruvkun, and their pivotal role in post-transcriptional gene regulation. This recognition follows the 2023 award to Katalin Karikó and Drew Weissman for their development of mRNA vaccines, underscoring the transformative impact of RNA research.
Since the 1960s, transcription factors were believed to be the primary regulators of gene expression, directing the production of mRNA from DNA. However, Ambros and Ruvkun’s groundbreaking work revealed an additional regulatory mechanism that occurs later in the protein synthesis process.
In 1989, while studying the nematode Caenorhabditis elegans, Ambros and Ruvkun both cloned the lin-4 and lin-14 genes, uncovering intriguing insights. Ruvkun demonstrated that mutations in the 3′ untranslated region (3’UTR) of lin-14 extended its protein expression beyond the normal stage, suggesting a post-transcriptional regulatory mechanism. Meanwhile, Ambros discovered that lin-4 produced small noncoding RNAs—later identified as microRNAs—that bind to complementary sequences in the 3’UTR of lin-14, suppressing its protein translation. These collaborative findings revealed a novel regulatory mechanism that was initially thought to be specific to nematodes but later proven to be conserved across many species.
In 2000, Ruvkun’s lab identified another microRNA gene, lin-7, and demonstrated its conservation across species, including humans. This discovery, coupled with subsequent research, established microRNAs as ubiquitous and critical regulators of gene expression across the animal kingdom, and even in viruses.
Today, scientists have identified over 1,000 human microRNAs and nearly 50,000 mature microRNA sequences across 271 organisms. These small molecules are recognized as essential regulators of cellular processes. The Nobel Prize honors Ambros and Ruvkun’s lasting contributions, which have profoundly shaped our understanding of gene regulation and hold immense potential to drive medical and biotechnological advances.
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