Subdued Initial Response
The results were published in Cell in 1993 and initially received little attention. However, interest grew in 2000 when Dr. Ruvkun’s research group published the discovery of another microRNA encoded by let-7.
In contrast to lin-4, let-7 was highly conserved and present throughout the animal kingdom. The article sparked great interest. In the following years, hundreds of microRNAs were identified. Today, researchers know that there are more than 1000 genes for various microRNAs in humans and that gene regulation by microRNAs is found in all multicellular organisms.
In addition to mapping new microRNAs, experiments by several research groups have elucidated fundamental mechanisms. Their binding leads to inhibition of protein synthesis or degradation of mRNA. Interestingly, a single microRNA can regulate the expression of many genes. Conversely, a single gene can be regulated by multiple microRNAs, thus coordinating and fine-tuning entire gene networks.
The cellular machinery for producing functional microRNAs is also used to produce other small RNA molecules in plants and animals, for example, as a means of protecting plants from viral infections. Andrew Z. Fire and Craig C. Mello, who were awarded the Nobel Prize in 2006, described RNA interference, in which specific mRNA molecules are inactivated by the addition of double-stranded RNA molecules to cells.
Small RNAs, Great Importance
Gene regulation by microRNA has likely existed for hundreds of millions of years. This mechanism has enabled the evolution of increasingly complex organisms.
From genetic research, it is known that cells and tissues do not develop normally without microRNAs. Abnormal regulation can lead to cancer. Mutations in genes encoding microRNAs cause, among other things, congenital deafness and eye and skeletal diseases. And mutations in one of the proteins required for microRNA production lead to the DICER1 syndrome, a rare but severe syndrome associated with cancer in various organs and tissues.
This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.