Double-stranded RNA (dsRNA) – RNA Virus Genomes

00:00 Alright, so that completes our discussion of the DNA viruses. Now let's turn to viruses with RNA genomes, and a few points about RNA, important to make here because this is a very different molecule. Only viruses have genomes of RNA. They can have DNA obviously, we’ve just talked about them, but no other thing on the planet has an RNA genome, except the virus. Cells have no way to copy an RNA molecule into another RNA, at least long RNA molecules.

00:32 They have no RNA-dependent RNA polymerase (RdRp), that’s the enzyme that would copy the RNA genome. Therefore that enzyme is always encoded in the RNA virus genome. So virus genomes always encode in RNA dependent RNA polymerase and that RNA polymerase copies the RNA genome and it also makes mRNA from the genome as well. So there is no cellular involvement in this process. The virus has to encode the RNA polymerase. Now in many of the slides we’re going to look at, I draw the RNA as a squiggly green line. Of course in reality, it's not that at all. Not only is it not green, but it has much more extensive structure than we ever show. And on the right of this slide is probably what most RNA molecules look like. They have extensive secondary structure. This is base pairing within the RNA sequence which you can see here as stem loops, but they also have tertiary structure, where the loop regions for example, can interact over long distances and you can see that happening here by these dotted lines between distal sequences. So RNA molecules are really highly folded up structures that absolutely do not resemble a line on a piece of paper.

01:50 Alright let's start with the viruses that have double-stranded RNA genomes. Just like the DNA viruses we can have double or single stranded. Viruses with a double-stranded RNA genome, interestingly they contain both the plus and the minus strand. They are double-stranded, and that plus strand would be the messenger RNA, but ribosomes cannot get at that plus RNA to translate it. So you have to make mRNA from these double-stranded RNA genomes. So the mRNA synthesis that is shown here in this slide, as the single green line with the shaded background, that reaction has to be done by a viral enzyme. Again the cell cannot make RNA from RNA, and because this reaction has to be the first thing that takes place in an infected cell, the enzyme that carries it out has to be in the virus particle. So this is going to be a theme we’re going to get back to over and over with these RNA viruses, some of them the RNA polymerase has to be in the particle, because the first step is the making of mRNA. For other viruses we don't have to have the polymerase in the particle and we will see why in a moment.

03:04 So back to these double-stranded RNA viruses, we’re making a messenger RNA that's then translated into protein by the cell, of course, and the proteins go on to produce new virus particles. And to make new genomes, some of those mRNAs are simply copied to make a minus strand by the viral polymerase. It’s a relatively simple replication strategy; you just have to remember that double-stranded RNA cannot be translated, even though it has a plus strand in it.

03:33 So the well-known double-stranded RNA containing viruses are the real viridae. They have about 10 double-stranded RNA segments. So these genomes are in pieces as you can see here, it's not one long DNA, although there are viruses with single double-stranded RNA genomes, and a very important human pathogen in this group are the Rotaviruses that cause human gastroenteritis.