Can pseudogenes control cancer?

05 March 2013

Interview with

Nell Barrie

Kat - And our final, kind of crazy gene RNA cancer story is about a gene called PTEN and this is a paper published in Nature Structural and Molecular Biology this week from scientists in the US. This is about pseudogenes which sound like kind of fake genes? What's going on here?

Nell - Well, this is interesting because essentially a pseudogene is a bit of DNA that's almost exactly the same sequence as a gene that's actually doing something, but it's changed slightly. And I guess probably what's happened there is it's got duplicated at some point during evolution. Because you've got two copies, you don't need both. So, an mutation in one of these copied genes isn't going to cause a problem. So you end up with a slightly mutated gene which becomes a pseudogene. Now obviously, the standard idea would be that this isn't actually doing anything. It's not coding in the right way for the gene. It's been mutated so it doesn't matter. It's just a piece of what we used to call 'junk DNA'.

Kat - But we're not allowed to say that anymore.

Nell - No, we're not allowed to say that anymore. And that's because it turns out that it could actually be doing something. So, it's not quite as simple as it first appeared.

Kat - So, what does it looks like it's doing? So, this is a pseudogene for a cancer gene called PTEN which is normally a tumour suppressor.

Nell - Yeah and I mean, the interesting thing here is that because it's so similar to PTEN, it's actually interfering with normal processes involving PTEN inside the cell. So for example, the pseudogene can actually suppress the promoter region for PTEN so essentially, that's turning it off. And it can also bind, soak up little pieces of microRNA that are meant to be interacting with PTEN. So, it's kind of subverting the normal processes by being such an almost exact copy within the cell.

Kat - I think it's really interesting putting this in the context of what we are now starting to understand about how the levels of gene activity are important. It's not so much about, "This gene is on. This gene is off." It's actually, "Do you have an extra dose? Are you making a bit more or a bit less?" And gene regulation is getting really complicated because it seems to be maybe about the subtle levels. So, perhaps that's playing a role here, but thanks very much Nell. 

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