Prof. Gary Ruvkun

Prof. Gary Ruvkun Winner of Wolf Prize in Medicine - 2014
Prof. Gary Ruvkun

From Massachusetts General Hospital and Harvard Medical School

Prof. Ambros and Prof. Ruvkun: MicroRNAs were discovered in 1993 by Victor Ambros during a study of the role of the gene lin-14 in the development of C.elegans, in parallel to the demonstration of the Ruvkun group that elements of the lin-4 gene product operate by acting on the 3’UTR of Lin-14, regulating its expression, at the level of RNA. It was indeed found that a short RNA product encoded by the lin-4 gene regulates the expression of the Lin-14 protein. In 2000 Ruvkun discovered the second microRNA characterized: let-7, which repressed lin-41, lin-14, lin-28, lin-42, and daf-12 expression during developmental stage transitions in C. elegans. let-7 was soon found to be conserved in many species, indicating the existence of miRNA as a wider phenomenon. Since 2000, miRNA research has revealed multiple roles in negative regulation (transcript degradation and sequestering, translational suppression) and possible involvement in positive regulation (transcriptional and translational activation) across the animal and plant kingdoms. In plants, miRNAs control the expression of genes encoding transcription factors, stress response
proteins, and other proteins that impact the development, growth, and physiology of plants. In the animal kingdom miRNAs are involved in most biological processes, playing a key regulatory role in gene expression in health and disease. . Different sets of expressed miRNAs are found in different cell types and tissues. These small endogenous miRNAs interact with a variety of important genes and play critical roles in a wide range of biological processes, including cell proliferation and differentiation. miRNAs are frequently dysregulated in human diseases including
numerous cancers. miRNAs are involved in cancer pathogenesis by regulating oncogenes or tumor suppressor genes. It is therefore anticipated that molecular diagnostics as well as therapies based on miRNA biology will be developed in the future, as is already apparent from the emerging scientific and clinically oriented lliterature.