MicroRNA - History

History

MicroRNAs were discovered in 1993 by Victor Ambros, Rosalind Lee and Rhonda Feinbaum during a study of the gene lin-14 in C. elegans development. They found that LIN-14 protein abundance was regulated by a short RNA product encoded by the lin-4 gene. A 61-nucleotide precursor from the lin-4 gene matured to a 22-nucleotide RNA that contained sequences partially complementary to multiple sequences in the 3’ UTR of the lin-14 mRNA. This complementarity was both necessary and sufficient to inhibit the translation of the lin-14 mRNA into the LIN-14 protein. Retrospectively, the lin-4 small RNA was the first microRNA to be identified, though at the time, it was thought to be a nematode idiosyncrasy. Only in 2000 was a second RNA 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 a wider phenomenon.