Is There an "Off Switch" for the Flu?

Uploaded by UniversityRochester on 23.08.2012

Unlike most organisms that use DNA,
Unlike most organisms that use DNA as its genetic material, influenza is a RNA-based virus.
And here in the Turner lab, we’ve sort of been focused on RNA structure
and the sort of forces that govern how RNA folds.
For a long time, our lab has been developing methods for predicting RNA structure from sequence.
And now there is a huge amount of genome information of sequence.
And so we’re trying to see can we take out interesting regions of an RNA and then predict the structure of that RNA.
So we though influenza would be a nice target for going after a virus because it has this sort of RNA genome.
And very little was known about the roles of RNA structure and influenza.
The RNA has 2 roles, really, in influenza RNA. One is that it carries the genetic information.
So it’s influenza’s equivalent of DNA in humans, in that sense.
And also it codes for proteins. So it tells what sequence protein to make.
So what we saw is that there’s interesting RNA structure at one of the sites,
and this forms what is called a pseudoknot, where basically the RNA folds into a complicated structure
and now this pseudoknot can actually be in sort of transition with another structure called a hairpin.
So you have a highly folded pseudoknot and a more accessible hairpin structure.
And essentially the transition between this hides or reveals different parts of what we call splicing factors.
So on the left hand side we’re seeing the results for the hairpin conformation.
And we think we have a switch.
Basically, you can turn the splicing off by having the pseudoknot or you can turn the splicing on by having a hairpin.
The switch that we discovered in influenza is part of a splice site.
And the idea of splicing is that you get one part of the RNA to throw away another piece of the RNA and combine to a third piece of the RNA.
It’s important to stop the splicing from taking place because one of these proteins, which require splicing,
is an essential protein. If the virus does not have that protein, it cannot propagate.
Another aspect that’s very interesting is ‘Can we affect this equilibrium?’
This is relevant for medicine. So the idea is if this is truly an off switch, and this is truly an on switch,
can you freeze the off switch or can you freeze the on switch by adding in a small molecule?
The research is important because there are implications for designing therapeutics to target influenza.
Most of us don’t get it because we get a vaccine, but there are still a lot of people who die, every year, from influenza infections.
The hope is that we can design small molecules that you could take as a pill,
and that would interfere with the reproduction of the influenza virus and therefore cure it.
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