This year’s Nobel Prize in Medicine goes to Victor Ambros and Gary Ruvkun. The two US researchers discovered the molecular class of microRNAs together in 1993 and elucidated what biological function these tiny RNAs fulfill. With their research on roundworms, they have discovered a fundamental mechanism of gene regulation that also occurs in other living beings, including humans. Thanks to the two researchers, we now know that microRNAs bind to messenger RNAs – the mRNAs – and thereby block the production of unneeded proteins. MicroRNAs are therefore responsible for the fact that different cell types can develop from our genetic material.
Whether skin cell, nerve cell or blood cell – every cell in our body inherently has the same genetic material and therefore the same information. For example, our DNA contains the building instructions for all the proteins that build our cells and regulate their function. Depending on the cell type, however, only the required information is retrieved from the DNA; everything else remains unused. Which proteins are actually produced is regulated by transcription factors, as researchers discovered in the 1960s. These proteins attach to the DNA and thus block or promote the reading of certain genes. But transcription factors alone could not explain the observed differences between cells.
RNA snippets prevent protein production
A few years later, Victor Ambros and Gary Ruvkun discovered a second, previously unrecognized mechanism of gene regulation using nematodes. In 1993 they realized that in addition to mRNA, which acts as a messenger molecule to transfer genetic information from DNA into proteins, there is another type of RNA molecule, so-called microRNAs. These are significantly shorter than mRNAs and do not contain instructions for building proteins. During their experiments, Ambros and Ruvkun also discovered that one such microRNA, lin-4, can prevent the production of a specific protein, lin-14. Unlike transcription factors, this gene regulation does not take place directly on the DNA in the cell nucleus, but in the cytoplasm. There, in the cell’s protein factories, the mRNA is normally read out with the corresponding protein construction instructions. However, by attaching itself to this mRNA, the microRNA prevents the protein from being made, the tests showed. The base sequence of the microRNA lin-4 matched exactly to a section of the mRNA of Lin-14.
Initially, the research world assumed that this microRNA was a special and exotic mechanism of nematodes. A little later, however, Ruvkun’s research team discovered another microRNA that blocked the formation of another protein. In contrast to Lin-14, this protein is found in numerous living beings. This discovery proved that such RNA snippets not only regulate the genes of nematodes, but are also found throughout the entire animal kingdom, including humans. For this discovery, the two will receive this year’s Nobel Prize in Medicine. “This groundbreaking discovery by Ambros and Ruvkun was unexpected and revealed a whole new dimension of gene regulation that is essential for all life forms,” explains the Nobel Prize Committee.
Basic understanding of gene regulation
Today, thousands of microRNAs are known to be in our genome. For many of them, the base sequence matches different mRNAs, so that they regulate the production of several proteins at the same time. Conversely, an mRNA can be blocked by several different microRNAs. This mechanism enables efficient and finely adjustable control of our gene activity and protein production. This is why there are so many different cells and types of tissue in our body. Some of these microRNAs also existed at an early stage of evolution and have been preserved from sponges and early unicellular organisms to humans; others only appeared in the course of evolution.
In contrast to mRNAs, whose use as vaccines was awarded the Nobel Prize in Medicine last year, there are currently no concrete uses for microRNAs in medicine. However, their discovery and understanding of their function are the basis for future research. “Fundamental understanding is the first step toward developing applications,” the Nobel Committee said. There are initial tests in the treatment of tumors, cardiovascular or kidney diseases. However, it has so far been a challenge to control the microRNAs so that they arrive at the desired tissue and exclusively fulfill the intended function without side effects.
Source: Nobel Committee for Physiology or Medicine, NobelPrize.org