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

翻译人员: Xiaoyu Ye 校对人员: Emma Gao

You can think of your cells

你可以把你的细胞想象成

as the kitchen in a busy restaurant.

繁忙的餐馆厨房。

Sometimes your body orders chicken.

有时候你的身体想点一份鸡肉。

Other times, it orders steak.

有时候它又会想点一份牛排。

Your cells have to be able to crank out

你的细胞得有能力制造出

whatever the body needs

身体需要的一切，

and quickly.

而且要快。

When an order comes in,

当点单出现后，

the chef looks to the cookbook, your DNA,

主厨开始翻阅菜谱，你的DNA，

for the recipe.

来查找配方。

She then transcribes that message

她然后将这个信息抄录

onto a piece of paper called RNA

到一张叫做RNA的纸上，

and brings it back to her countertop, the ribosome.

并将RNA带到她的工作台上——核糖体。

There, she can translate the recipe into a meal,

在那里，她可以用菜谱做成美味的一道菜，

or for your cells, a protein,

对细胞来说就是一种蛋白质。

by following the directions that she's copied down.

这一切只要按照抄录的菜谱就可以了。

But RNA does more for the cell

但细胞中的RNA

than just act as a messenger

不仅仅是一个信号传递者，

between a cook and her cookbook.

在厨师和他的笔记之间

It can move in reverse and create DNA,

它可以反向生成DNA，

it can direct amino acids to their targets,

它可以指导氨基酸到达其它目标位置，

or it can take part in RNA interference,

它也可以在RNA干扰中发挥作用，

or RNAi.

这种RNA称作沉默RNA（RNAi）。

But wait!

等等！

Why would RNA want to interfere with itself?

为什么RNA想干扰它自己呢？

Well, sometimes a cell doesn't want to turn

有时候细胞并不想

all of the messenger RNA it creates into protein,

将所有的信使RNA都翻译成蛋白质；

or it may need to destroy RNA injected into the cell

有时候它需要把被病毒入侵的细胞的RNA

by an attacking virus.

消灭掉来摧毁掉病毒。

Say, for example, in our cellular kitchen,

比如，在我们的细胞厨房中，

that someone wanted to cancel their order

有人想取消订单，

or decided they wanted chips instead of fries.

或者决定用炸薯条替代油炸小鱼。

That's where RNAi comes in.

这时候沉默RNA就发挥作用了。

Thankfully, your cells have the perfect knives

幸好你的细胞有合适的刀具

for just this kind of job.

能胜任这样的工作。

When the cell finds or produces

当细胞发现或产生了

long, double-stranded RNA molecules,

长双链RNA分子，

it chops these molecules up

它将这些分子用

with a protein actually named dicer.

称作切酶的蛋白质切成小段。

Now, these short snippets of RNA

现在这些小段RNA

are floating around in the cell,

在细胞中漂浮着，

and they're picked up by something called RISC,

并被称作“RNA沉默复合体”发现，

the RNA Silencing Complex.

简称RISC。

It's composed of a few different proteins,

它由几个不同的蛋白组成，

the most important being slicer.

最重要的就是切酶。

This is another aptly named protein,

这个蛋白的名字也很合适，

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

我们很快就会知道为什么。

RISC strips these small chunks

RISC把这些小块的

of double-stranded RNA in half,

双链RNA拆成两份，

using the single strand to target matching mRNA,

用单链来匹配目标mRNA，

looking for pieces that fit together

寻找着合适的另一半，

like two halves of a sandwich.

就像三明治的两半。

When it finds the matching piece of mRNA,

当它找到匹配的mRNA，

RISC's slicer protein slices it up.

RISC的切割蛋白把它切掉。

The cell then realizes

然后细胞会发现

there are odd, strangely sized pieces

这些奇特古怪的RNA片段

of RNA floating around

四处飘荡，

and destroys them,

然后摧毁它们

preventing the mRNA from being turned into protein.

以阻止mRNA翻译成蛋白质。

So, you have double-stranded RNA,

所以当以有双链RNA时，

you dice it up,

你会把它切开，

it targets mRNA,

它匹配mRNA，

and then that gets sliced up, too.

然后那一段也会被切掉。

Voila!

瞧！

You've prevented expression

你阻止了错误的表达，

and saved yourself some unhappy diners.

避免自己吃一顿难吃的餐。

So, how did anybody ever figure this out?

那么这个是怎么被发现的呢？

Well, the process was first discovered in petunias

这个过程首先被发现在南美矮牵牛花中，

when botanists trying to create deep purple blooms

当植物学家试着创造深紫色花朵时，

introduced a pigment-producing gene into the flowers.

他们引入了一段色素基因进入细胞。

But instead of darker flowers,

但他们没看到颜色更深的花朵，

they found flowers with white patches

却只看到了白色，

and no pigment at all.

全然没有色素出现。

Instead of using the RNA produced by the new gene

花朵并没有使用新基因产生的RNA

to create more pigment,

来生成色素，

the flowers were actually using it

实际上这些花在用产生的RNA

to knock down the pigment-producing pathway,

来敲除色素生成通路，

destroying RNA

用沉默RNA摧毁了

from the plant's original genes with RNAi,

来自植物自己基因的RNA，

and leaving them with pigment-free white flowers.

最终这些花都是无色素的白花。

Scientists saw a similar phenomena

科学家还在一种小型蠕虫——线虫的体内

in tiny worms called C. elegans,

发现了类似的情况。

and once they figured out what was happening,

当他们弄明白发生了什么以后，

they realized they could use RNAi

他们意识到可以用沉默RNA

to their advantage.

来帮助他们。

Want to see what happens

想看看

when a certain gene is knocked out of a worm

特定基因被敲除以后的蠕虫或者苍蝇

or a fly?

长什么样吗？

Introduce an RNAi construct for that gene,

构建一段针对相关基因的沉默RNA，

and bam!

砰！

No more protein expression.

再也不会表达相关蛋白了。

You can even get creative

再创造性一点，

and target that effect to certain systems,

你可以针对特定系统敲除基因，

knocking down genes in just the brain,

可以在大脑中，

or just the liver,

在肝脏中，

or just the heart.

或者在心脏中。

Figuring out what happens

弄清敲除

when you knock down a gene in a certain system

某个系统的特定基因的效应

can be an important step

是了解这段基因功能的

in figuring out what that gene does.

重要的一步。

But RNAi isn't just for understanding

然而沉默RNA不仅可用来

how things happen.

理解事情的发生。

It can also be a powerful, therapeutic tool

它也可以成为一个强大的治疗工具，

and could be a way for us to manipulate

也可以成为我们控制细胞内部的

what is happening within own cells.

一种方法。

Researchers have been experimenting

研究者们已经开始试着

with using it to their advantage in medicine,

用它来改进药物，

including targeting RNA and tumor cells

包括瞄准特定RNA和肿瘤细胞，

in the hopes of turning off cancer-causing genes.

希望能关闭致癌基因。

In theory, our cellular kitchens

理论上，我们的细胞厨房

could serve up an order of cells,

可以处理细胞的订单，

hold the cancer.

并阻止癌症。