This was written in 2004, off the top of my head, and it's not a field I'm an expert in, so it's undoubtedly inaccurate to some extent. I know I left out some important people, for example. It will also certainly become dated pretty quickly, if I leave it up at all.
I wrote this because I realized that this really amazingly cool and genuinely paradigm-shifting stuff really hasn't got much play in the general media, though it's been heavily --appropriately heavily -- publicized in the scientific presses. This was Science's "Breakthrough of the Year" for 2002, and one of their Top Ten in 2003.
The background is the Central Dogma -- DNA leads to RNA leads to protein, a concept proposed (explicitly without definitive data -- that's why it's "dogma") by Francis Crick in the 1950s. Over the years the Central Dogma has weakened somewhat (reverse transcriptase means RNA -> DNA, for example), but mostly the things that were found fit into the general picture. There are plenty of different kinds of RNA -- mRNA, that's translated into protein, is actually a small minority in the cell -- but again it's part of the general picture. Ribosomes have lots of RNA, tRNA has lots of RNA, but they're components of the protein translation pathway. There are other variations -- RNA with enzymatic activity, for example -- but by and large they are lab curiosities that apparently don't normally play a major role in the cell.
MicroRNAs are different. They don't fit into the Central Dogma particularly well, they work differently from other RNA forms, and it really looks as if they're real: they're found in cells, they do critical stuff, they're common and important.
This is kind of a three-part story. The first part was found in worms, flies, and plants; the second and third were found in mammals.
The first finding was at first apparently another RNA curiosity. It was found that RNA in a double-stranded form (double-stranded RNA, dsRNA) (like DNA in the genome; dsRNA is found in some viruses, but it was considered an unusual and minor form in eukaryotic cells) could lead to a surprising "silencing" effect in C. elegans, a worm used in lots of research. Silencing means that the gene whose sequence matched that of the dsRNA was turned off -- very powerfully turned off, so that none remained. The same phenomenon was found in flies and in plants (it's slightly different in plants; but the principles seem to be the same).
Lab curiosity? But the effect was so strong and, it turned out, so specific -- so precisely targeted to one single gene -- that it seemed odd to be a test-tube phenemenon. Careful examination showed that it's not. In worms, in flies, in plants, this is an important way certain genes are regulated. In plants, it turns out to (among other things) be a form of immunity to plant viruses. Viruses have RNA. Plants take the RNA and generate dsRNA from that. That silences the virus. Happy plants. (Except that viruses are smarter than that, and there is now a rapidly-increasing number of instances of viruses that have anti-silencing mechanisms.)
As well as being a real thing in worms, it still works as an artificial system. You can imagine how useful it is to be able to specifically silence a single gene, for research purposes; and this is faster, cheaper, and easier than any other way. Wouldn't it be nice if it worked in mammalian cells as well? You have exactly the same needs there, but more so, because it's much harder to knock out single genes in mammals, even in mice. But this didn't work in mammalian cells, for the most part. Injecting in dsRNA does all kinds of terrible things: because for mammalian cells, the only thing that has dsRNA is a virus, and mammalian cells react ferociously and suicidally to a virus infection.
But it was so potentially useful that it justified a lot of testing, and a few years ago (2001, I think) a couple of groups found the trick. Long dsRNA looks like viruses, but if it's short enough, say less than 30 base pairs, then the cell doesn't react as if it's a virus -- and you still get the silencing effect. (That was Tom Tushl's work, and he's another guy in line for the Nobel.)
Bingo. Over 2000 papers published since (including two of mine) have used that trick.
But the same question arose. If this trick works so spectacularly well, and so specifically, in mammalian cells, can it really just be a research trick? Maybe the mammalian cell already uses the small double-stranded RNAs for something.
But wouldn't we have found it? Not necessarily. These are small, and the techniques that were out there don't look at tiny things like this -- miRNAs would be thrown out as contaminants. So a few groups went hunting in the genome and ... well, day-um. The genome is riddled with small, double-stranded, less-than-thirty-base-pair, RNAs. Hundreds, maybe thousands, of them. MicroRNAs are important regulatory elements in mammalian cells. Who knew?
A whole new world, tucked away for millenia in our genomes, and no one found it until two years ago, when they actually predicted it was there and went specifically, specially hunting for it. Okay, I'm a geek, but it gives me chills.