Dr Julie Claycomb, University of Toronto
Kat - Everyone’s heard of DNA, or deoxyribonucleic acid to give it its full name - the blueprint of life that encodes the information that tells our cells when to grow, what to be and when to die. But there’s another important player in the world of molecular biology, and that’s RNA, or ribonucleic acid.
It’s becoming increasingly clear that RNA plays a vital role in many different biological processes in all kinds of organisms, from viruses and bacteria to insects, worms, plants and mammals. Tiny RNAs can even control the activity of our genes - something that researchers are now trying to exploit to come up with treatments for cancer and other diseases. I spoke to Dr Julie Claycomb at the University of Toronto to get the low-down on these mysterious molecules.
Julie - RNA is a cousin of DNA. It’s a type of nucleic acid and it’s really the go-between between the instructions to make proteins, which are your DNA in the nucleus of your cell, and proteins. So, DNA is turned into RNA, a copy of itself and then the RNA is translated into proteins which make up all of you – your skin, your hair, everything.
Kat - We think of this as the central dogma of molecular biology that DNA encodes RNA and these makes proteins, but now we know that RNA is a little bit more complicated. What do we know about RNA now?
Julie - So, in addition to this RNA that’s the go-between between DNA and proteins, we have these itsy-bitsy RNAs, these small RNAs that are utilised by the cells to regulate the expression of those bigger messenger go-between RNAs.
Kat - What do we call these little RNAs?
Julie - Yes, so these little RNAs are called small interfering RNAs or microRNAs and it just depends on where they’ve originated from what we call them. So, the cell makes these microRNAs that regulate gene expression.
Kat - So, the instructions to make these microRNAs, they're still in our DNA as well.
Julie - Absolutely, yeah. These microRNAs are encoded in our genomes and in fact, they're encoded in the genomes of lots of different organisms ranging from plants all the way to humans. So, this is a very evolutionarily conserved mechanism for regulating gene expression.
Kat - What are they normally doing in our cells?
Julie - So normally, they're regulating the levels of gene expression. What they can do is that they can actually cause the inhibition of generating a protein from that messenger RNA.
Kat - So, like switching it off.
Julie - They turn it off basically. They inhibit it from becoming what it’s meant to instruct which is the making of a protein. In addition in some instances, these small RNAs can induce the degradation, the altogether destruction of those messenger RNAs. And again, keep them from being turned into a protein or keep them from being expressed as we say.
Kat - Sometimes we might think about a gene that’s making protein and then suddenly, we have this whole level of regulation on top of that. So, are these really playing an important role in how our genes are switched on and off?
Julie - Yeah, absolutely. These microRNAs have been implicated in cancer. They're very important for normal development and there are a number of instances in which microRNAs becoming misregulated or mutated leads to aberrant gene expression and the onset of cancer. So, they're absolutely a very key player in regulating gene expression throughout development and in our normal cell division.
Kat - So, if these microRNAs are helping to control which genes are on and off, what's controlling them?
Julie - So, microRNAs are transcribed just as normal genes, mRNAs, are. They're expressed in the cell using the same types of machinery and we still have a lot to learn about what temporally controls which microRNAs are expressed when and in which cell types because there are different types of microRNAs that are expressed in different cell types. So, they're expressed in much the same way as most of your mRNAs, your normal protein coding genes are. They're then processed by a number of other protein machines to make them their small size which is about 20 nucleotides on average.
Kat - So they get chopped up and then go and do their job.
Julie - Yeah, absolutely. They get chopped up. They start as a much longer – we call it a transcript – a much longer molecule which is then processed into several iterations, several shorter molecules. And ultimately, the small RNA is bound by a protein called the Argonaut protein which is the effector molecule, the machine that actually causes mRNA degradation or causes the inhibition of the production of proteins.
Kat - I remember when I was doing my PhD back in the day, this was some time ago, that this field really started to take off because they first really found this was going on in little worms, which is what you work in. Tell me a little bit about the history of where we’ve come from since those first discoveries.
Julie - Plants and worms have both been very, very important in the key discoveries that led us to understanding how RNA interference and microRNAs work. Basically in plants, one of the things they first discovered was that if you added a colour gene to make the plants more purple, lo and behold! The plants turned less purple. So, there was a process on-going in the plant cells that shut off gene expression and this process came to be known later as co-suppression. In C. elegans, what was found, there were several different discoveries. One of which was in the early ‘90s that there were these small RNAs - they didn’t know they were small RNAs at that time - that led to defects in developmental timing. Subsequently, through a lot of different studies, people identified microRNAs, the loci on the chromosomes encoding these small RNAs, and through technological advances, we’ve done a lot of identification of these microRNAs and other small RNAs in the worm.
Kat - So, we know that these short RNAs are really important for normal life, normal growth, normal cells to function. But now, we’re starting to exploit them. Tell me about some of the things we can do to use this knowledge for our benefit.
Julie - Yes, so surely you can imagine a situation if we could selectively shut off genes that were bad for us, that were deleterious to us that we could then somehow eliminate or reduce disease, right? So, for instance, cancer is often caused by the misexpression of a number of genes which then lead to overdivision of the cells, overproliferation of the cells. If we could turn off those genes that tell a cell to divide and divide, and keep dividing, then we could potentially stop cancer progression. So, as you might imagine, RNA interference and these small interfering RNAs are a very hot topic of interest in therapeutics. So, if we could find a way to exploit them then we could potentially develop new therapeutic mechanisms.
Kat - That was Dr Julie Claycomb from the University of Toronto.