Victor Ambros and Gary Ruvkun just won the 2024 Nobel Prize in Medicine for the discovery of microRNA (miRNA). Many people have not heard of miRNA. In 1993, two research groups led by Dr. Ambros and Dr. Ruvkun both published in the same issue of Cell that a small RNA called lin-4 was essential to larval development of Caenorhabditis elegans, a 1 millimeter long worm. - They noticed the sequence of lin-4 was complementary to the mRNA sequence of the 3'UTR of lin-14, a protein playing a key role in C. elegans larval development, and lin-4 itself was unlikely to encode a protein. + They noticed the sequence of lin-4 was complementary to the mRNA sequence of the 3'UTR of lin-14, a protein playing a key role in C. elegans larval development, and that lin-4 was unlikely to encode a protein. They found similar sequences in other nemotode species, and hypothesized that lin-4 downregulated lin-14 through RNA-RNA interaction.
A small loop of non-coding RNA is clipped by enzymes forming 2 short (approximately 22 nucleotide) complementary strands of RNA. These are incorporated into a protein known as Argonaute (AGO), which keeps one strand and ejects the other, and then undergoes conformational change and becomes known as the RNA-induced silencing complex (RISC).