This is not the first Nobel Prize awarded for research related to this shortest and most recently discovered ribonucleic acid. In 2006, Andrew Z. Fire and Craig C. Mello received the Nobel Prize for discovering "the phenomenon of RNA interference or silencing gene activity by double-stranded RNA." Although the term microRNA did not appear in that one-sentence description of their scientific achievement, both previous and current Nobel laureates are connected by this same type of ribonucleic acid—microRNA (also known as miRNA or µRNA).
For years, it has been known that cells of a given organism, including humans, share the same set of genes but differ in structure and function due to the highly variable regulation of gene activity. Some genes are activated while others are silenced, meaning that the levels of proteins encoded by these genes vary across different cell types. For several decades, it was believed that transcription factors—proteins capable of recognizing specific genes—were responsible for regulating gene activity. This process leads to variable levels of different mRNAs coded by various genes, resulting in diverse protein synthesis during translation.
However, in the 1980s and 1990s, another mechanism of gene regulation was discovered that operates post-transcriptionally. The new regulators of gene activity turned out to be previously unknown small molecules called microRNAs, ranging from 21 to 25 nucleotides long. In comparison, previously known shortest RNA molecules (tRNA or transfer RNA) range from 75 to 95 nucleotides. MicroRNA molecules bind to mRNA produced during transcription and activate protein complexes called RISC, capable of degrading mRNA or halting translation. In both cases, the final effect is the same: inhibition of translation and a significant reduction in protein levels produced during this process. In other words, eukaryotic cells (i.e., those with a nucleus) have a gene silencing system that can destroy their own mRNA and controlably lower protein levels produced during translation. It is worth noting that the mechanism through which microRNAs regulate gene activity likely emerged about a billion years ago as a way to protect primitive cells from viruses. One hypothesis suggests that over time
this silencing mechanism began to serve additional functions related to regulating cellular gene expression.
Research conducted after 2006 confirmed that microRNAs and post-transcriptional regulation of gene activity are universal phenomena present in all multicellular organisms; initially, however, the model organism was only a small roundworm called Caenorhabditis elegans (shortened to C. elegans). These studies demonstrated that disturbances in microRNA biogenesis could be significant in the etiology of various diseases, ranging from cancers to diabetes and neurodegenerative or autoimmune diseases. To date, over 1,000 different human microRNA molecules have been identified that can regulate thousands of our genes. It is estimated that microRNAs can inhibit the activity of between 5,000 to 12,000 human genes (these are only approximate figures). Furthermore, one type of microRNA can bind to many different mRNA molecules (up to 200), while several different microRNAs can bind to a single specific mRNA strand.
Since 2006, research on the activity and mechanisms of action of microRNAs has significantly expanded; new observations have emerged regarding the "export" mechanism of microRNA molecules from one cell to distant tissues and cells. MicroRNAs execute this "descent" by being packaged into lipid vesicles called exosomes within cells; exosomes are secreted outside the cell into the bloodstream, from where they can enter recipient cells. This mechanism somewhat resembles hormone action.
It is not an exaggeration to state that microRNAs are fundamental for the development and functioning of organisms, including humans. It cannot be ruled out that future research on new types of RNA other than microRNAs will also be honored with another Nobel Prize..
