RNAi: Slicing, dicing and serving your cells - Alex Dainis

You can think of your cells

as the kitchen in a busy restaurant.

Sometimes your body orders chicken.

Other times, it orders steak.

Your cells have to be able to crank out

whatever the body needs

and quickly.

When an order comes in,

the chef looks to the cookbook, your DNA,

for the recipe.

She then transcribes that message

onto a piece of paper called RNA

and brings it back to her countertop, the ribosome.

There, she can translate the recipe into a meal,

or for your cells, a protein,

by following the directions that she's copied down.

But RNA does more for the cell

than just act as a messenger

between a cook and her cookbook.

It can move in reverse and create DNA,

it can direct amino acids to their targets,

or it can take part in RNA interference,

or RNAi.

But wait!

Why would RNA want to interfere with itself?

Well, sometimes a cell doesn't want to turn

all of the messenger RNA it creates into protein,

or it may need to destroy RNA injected into the cell

by an attacking virus.

Say, for example, in our cellular kitchen,

that someone wanted to cancel their order

or decided they wanted chips instead of fries.

That's where RNAi comes in.

Thankfully, your cells have the perfect knives

for just this kind of job.

When the cell finds or produces

long, double-stranded RNA molecules,

it chops these molecules up

with a protein actually named dicer.

Now, these short snippets of RNA

are floating around in the cell,

and they're picked up by something called RISC,

the RNA Silencing Complex.

It's composed of a few different proteins,

the most important being slicer.

This is another aptly named protein,

and we'll get to why in just a second.

RISC strips these small chunks

of double-stranded RNA in half,

using the single strand to target matching mRNA,

looking for pieces that fit together

like two halves of a sandwich.

When it finds the matching piece of mRNA,

RISC's slicer protein slices it up.

The cell then realizes

there are odd, strangely sized pieces

of RNA floating around

and destroys them,

preventing the mRNA from being turned into protein.

So, you have double-stranded RNA,

you dice it up,

it targets mRNA,

and then that gets sliced up, too.

Voila!

You've prevented expression

and saved yourself some unhappy diners.

So, how did anybody ever figure this out?

Well, the process was first discovered in petunias

when botanists trying to create deep purple blooms

introduced a pigment-producing gene into the flowers.

But instead of darker flowers,

they found flowers with white patches

and no pigment at all.

Instead of using the RNA produced by the new gene

to create more pigment,

the flowers were actually using it

to knock down the pigment-producing pathway,

destroying RNA

from the plant's original genes with RNAi,

and leaving them with pigment-free white flowers.

Scientists saw a similar phenomena

in tiny worms called C. elegans,

and once they figured out what was happening,

they realized they could use RNAi

to their advantage.

Want to see what happens

when a certain gene is knocked out of a worm

or a fly?

Introduce an RNAi construct for that gene,

and bam!

No more protein expression.

You can even get creative

and target that effect to certain systems,

knocking down genes in just the brain,

or just the liver,

or just the heart.

Figuring out what happens

when you knock down a gene in a certain system

can be an important step

in figuring out what that gene does.

But RNAi isn't just for understanding

how things happen.

It can also be a powerful, therapeutic tool

and could be a way for us to manipulate

what is happening within own cells.

Researchers have been experimenting

with using it to their advantage in medicine,

including targeting RNA and tumor cells

in the hopes of turning off cancer-causing genes.

In theory, our cellular kitchens

could serve up an order of cells,

hold the cancer.