Viruses

Viral RNA contains the blueprints for all of the components of a particular virus. Examples of RNA viruses include the flu, polio, measles, and SARS.

A virus is a collection of genetic material (DNA or RNA) inside a protein shell. There is much scientific debate about whether viruses are alive. Like living creatures, they carry genes and evolve. But they are unable to reproduce on their own and must infect living cells and hijack cellular machinery (such as ribosomes) in order to copy themselves.

Though viruses are tiny, they are fierce. Influenza (the flu) alone has killed tens of millions of humans in the last 100 years.

Viruses carry their genetic information as either DNA or RNA. RNA is less stable and more prone to mutation than DNA, so RNA viruses generally change and evolve faster. This sometimes allows RNA viruses to jump from species to species (notable recent examples include the avian flu and swine flu, which jumped to humans from birds and pigs, respectively).

Viruses hijack cellular machinery in many ways, but in almost all cases, the virus tricks the cell into treating the virus’s genetic information as its own and transcribing and/or translating it. In those instances, perhaps the best way the cell can defend itself is to learn to recognize and destroy viral genes.

pRNA, a component of the strongest nanomotor on Earth, packs genetic information into a virus’s protein shell.

When a virus hijacks a cell, it forces the cell to produce copies of the virus. This process includes creating capsids—the outer protein shell of a virus. The genetic information of some viruses is so long and complex that it has to be folded and packed tightly to fit inside the capsid. This requires energy—it’s like trying to put a Jack-in-the-box back inside the box.

The energy comes in the form of ATP (adenosine triphosphate), a molecule that stores energy in the bonds between its atoms. ATP acts like a rechargeable battery, carrying energy throughout the cell to power its molecular machines. But to deliver the energy, ATP needs something to bind to.

This is where pRNA, or packaging RNA, comes into play. pRNA molecules together with ATPase motors bind ATP molecules and extract their energy. By using this energy, pRNAs form a ring that acts like a gear in a powerful motor, stuffing the genetic strands into the capsid and assembling the virus.

The RNA chopper and RNA destroyer are parts of a cell’s pathway for recognizing and destroying viral RNA.

In the Virus chapter of NOVA’s RNA Lab game, the process used to fight invading viruses is based on an immune response observed in bacteria, plants, and some animals (but not yet in humans) called RNA interference (RNAi). RNAi has two main steps.

RNAi Step 1: Intruder detection
Specially evolved RNAs and proteins detect strands of invading viral RNA and chop them up.

RNAi Step 2: Border guards
Another set of RNAs and proteins pick up some of the chopped-up viral RNA from Step 1. You can think of them as setting up security checkpoints near a cell’s ribosome, where translation occurs. These molecular border guards compare incoming messenger RNA (mRNA) that comes from either the virus or the host cell against their small pieces of the virus’s genetic code. Anything that matches codes for something that the virus is trying to make, so they slice it up before it gets through.

The “RNA chopper” in the NOVA RNA Lab stands in for the whole group of RNAs and proteins involved in Step 1—detecting and chopping up invading viral RNA. This design is modeled on an RNA found in mosquitoes that helps identify invading RNA from the dengue virus.

Cells can sometimes use a process similar to RNAi to quickly turn off their own genes. The ”RNA destroyer” that players design in the NOVA RNA Lab comes from an RNA involved in one such process in nematodes (roundworms). This RNA (called microRNA or miRNA) finds nematode mRNA with a matching sequence and signals to proteins that they should destroy this mRNA. This silences the target gene because its mRNA is destroyed before it is translated to make a protein.

NOVA’s RNA destroyer is doing double duty in a way that probably wouldn't happen in real cells—our RNA destroyer is both detecting viral mRNA and cutting it up. Proteins would normally carry out the actual destruction/cutting.

A special class of RNAs called “riboswitches” can switch from one shape to another when they detect specific molecules.

When it comes to riboswitches, the structural weakness of RNA is its greatest strength. Because some of RNA’s bonds (such as U-Gs) are weak, they can easily break and allow the RNA to transform. Molecules like DNA and proteins can’t transform as easily or as drastically as RNA, because their structures are much more stable.

Riboswitches “switch” shapes when they detect a specific molecule. Their 3D shape fits that molecule in such a way that they naturally bind to it. But binding to the molecule changes the way that RNA folds, because some of the base pairs will no longer be able to reach each other. This means that the RNA breaks some of its bonds and takes on a new 3D shape. Since molecular shape determines molecular function, that RNA now has a different function in the cell.

It’s like the effect that the light of the full moon has on a werewolf.* Just by being exposed to moonlight, a harmless human undergoes a rapid transformation to a feral creature. Riboswitches do not become monsters, but their transformations are swift, easily triggered, and functionally drastic.

The processes shown in the last two sections of the Virus chapter in NOVA's RNA Lab are not yet being used for medicine, but they demonstrate a possible, and promising, future treatment that could fight viruses, cancer, and who knows what else.

Here’s a simplified version of how it might work. Let’s say you want to design an RNA-based treatment for HIV (the virus that leads to AIDS).

Step 1: Identify a molecule that is only present in cells that have been infected by HIV. We’ll call it Molecule X.
Step 2: Design a riboswitch that can detect Molecule X by binding to it and switching shape.
Step 3: Tweak your RNA switch so that when it switches to its second shape, that shape activates “cell death.” Cell death is a natural process that your body already uses to eliminate sick cells.

The same principle might be used to fight cancer—but instead of finding Molecule X, the RNAs look for Molecule Y, which is only found in cancerous cells.

And why stop with just one RNA switch at a time? Why not design a whole RNA computer with many different RNA switches that can look for many different molecules in the cell and respond accordingly?

Perhaps RNA engineers could program a single RNA computer that fights viruses, defeats cancer, and trims out genetic defects from DNA. It sounds fanciful, and may be decades away, but scientists are exploring this as a real possibility. And if it works, it will change the world.