Quirks and quarks10:29Nobel Prize for understanding how genes are turned on and off
Gary Ruvkun says microRNAs, which are molecules that control how genes form our cells, could be the key to improving the way humans fight disease and even finding signs of extraterrestrial life.
On Monday, the Nobel Prize in Medicine or Physiology was awarded to Ruvkun and his colleague Victor Ambros for their discovery in 1993 of a group of previously unrecognized molecules (called microRNAs) that help control which genes are active and when. This plays a very important role in how complex life forms grow and function.
Gary Ruvkun is a professor of genetics at Harvard Medical School. spoke with Quirks and quarks host Bob McDonald about his life-changing discovery and how he hopes to use RNA to find life on other planets. Here is part of that conversation.
What was it like getting that call from Stockholm?
It's been in play for about 20 years. And so, at four in the morning, when the phone rings, it took me a minute to register, and my wife answered and said, “He has a Swedish accent!” Then it was like “Oh!”
Tell me the story of how we began to understand how genes are turned on and off. [which] led to his work on microRNA.
So this came up when doing genetic analysis on this little guy. [worm called a] nematode. So the nematode is a big part of the soil ecosystem and it is so simple that it has 959 cells and each cell has a name. So I started working in 1982, like Victor Ambros, and we worked together on the pedigree of the cells generated by the animal.
How did that lead to the discovery of the role of microRNA?
When we found out what these genes were, it turned out that one of them encoded a product that was about five times smaller than any gene had ever been seen to be. It was only 25 nucleotides (the building blocks of RNA and DNA) long. And that was a new phenomenon, and it was considered some kind of quirk, and it wasn't clear what it really meant.
When did you realize that this was a completely new genetic molecule?
These are the first days. At that time we didn't have any genomes, but within five years, genomes were emerging. The way we discovered that [microRNA was present in the human genome] We got a second one of these microRNAs, these very small genes, and that one had a human being? [equivalent]and I got an answer by comparing the worm's genome with its 25 letters, and there were those same 25 letters in the human genome.
What do these microRNAs actually do?
They regulate other target genes, carry out all kinds of different processes, and are used in essentially all animals and plants. They are as old as the divergence of plants and animals, which occurred a billion years ago. And they have been involved, for example, in the domestication of corn 5,000 years ago.
These mutations are those selected by indigenous peoples. They didn't know they were doing that, but they got what are called heterochronic mutants, mutants that do things differently when they are developing. And that's what makes corn cobs bigger.
I understand that more recently you have been applying your knowledge to the search for microbial life outside of our photovoltaic system. Tell me about that.
Yes, that has been a passion. So we dove into the richness of RNA biology and there's a long tradition of people trying to figure out how the ribosome works, for example.
And the ribosome is the little machine in all of our cells that takes messenger RNA and translates it into proteins, and it turns out that the key element of the ribosome is an RNA that probably existed before proteins even evolved.
That RNA is the most conserved thing on Earth, and that's how biologists around the world visit strange ecosystems like snow and ice, ponds, the deep ocean, or human feces, you name it. You can look up who is there by looking for the DNA segments that are present on the ribosome.
So I've been trying to convince NASA that this is how they should look for life on Mars, and their response is always, “Well, yes, but that's a very Earth-centric view.” to search for life. Are you stupid?” And my answer is: I would be stupid not to look for that first.
If you think that there will be life on Mars that evolved independently, that's stupid, because of course it will spread between Earth and Mars. They are very close to each other and there is a meteoric exchange between the two. We have Martian meteorites on Earth, not many, but it doesn't take many for bacteria to move between planetary systems.
Are there any future applications of microRNA research that you hope to see?
Yes. I mean, we're going to continue working on what the paths are right now. One of the most important things we do is that we now know a lot about what proteins are involved in presenting these small RNAs to their targets.
And we know that some of those proteins are not present in humans or in most of the animal kingdom, but worms have them, ticks and spiders, corals, and these are the organisms that defend antivirals much better. than us.
So we're trying to figure out why so many animals, like most insects, all vertebrates, essentially abandoned their old antiviral pathway to develop what's called the interferon pathway, which is how we fight viruses. And my opinion is that, in comparison, we don't do as good a job.
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