Translator: Hideki Yakushiji Reviewer: Claire Ghyselen
Good morning.
I am a cell biologist from RIKEN Yokohama.
Today I am going to tell you about junk.
Gomi! Yes.
Junk can be considered as something useless
or serving no purpose.
Let me give you an example.
A food that is considered having very little nutrition value,
we call that junk food.
Or you open our post box, and you find piles of advertisements,
we call that junk mail.
But you might be wondering
why a scientist is going to tell you about junk today.
I am not going to talk about any ordinary junk
but junk that is found inside our DNA.
DNA can be found inside our cells and they are the blueprints of life.
DNA contains all the genetic information that help us to start life,
to maintain our life, protect our life, and even end our life.
But there is a mystery hidden behind our DNA.
All of these processes that I just described to you
are controlled by genes.
But our genes can only be found in 2% of our DNA.
But there is more.
If you were to take DNA and extract it from your cell
from single cell of your body,
and you stretch out your DNA as long as you can,
that can be as long as two meters long.
What is more amazing is that if you were to take DNA
from all of the cells in our human body,
and combine them all together, and stretch it as far as you can,
it will go from this earth to the sun and back 200 times.
That’s the amount of DNA that we are carrying inside our body.
But as I said, this 2% can only be found
to describe the most important part of the genetic controls in our life.
You will be wondering how about this remaining 98%,
this non-coding regions of our DNA.
For the longest time, ever since the 1970s,
many scientists thought that this part of our DNA was considered junk or useless.
And that really got me curious
because when I first heard this as a high school student in biology class,
something didn’t really feel right.
You know, I didn’t feel good that I was carrying all this junk in my body,
and something had to be more than just uselessness.
So, that really got me curious and want to venture into my research.
I wanted to understand what is hidden behind this part of our DNA.
Over the past several years,
our lab and many other labs around the world have discovered
that there is far more information hidden in this area than previously thought.
DNA actually is not two dimensional linear.
But inside our cells, they can actually form
three dimensional interactions.
And what has been shown is that these non-coding regions of our DNA
are in close contact with the protein-coding regions
to regulate the gene expression.
They can switch on or switch off the gene.
What’s far more interesting is that many of the mutations,
the changes that occur in our DNA that can cause disease
are also found in this non-coding region of our DNA.
Mutations that can cause cancer, or autoimmune disease,
or Alzheimer’s or Parkinson’s,
these mutations are found in the non-coding DNA regions
and they are actually interfering [with] the control of the central genes to life.
And by these mutations,
we are finding very devastating consequences to our daily activities.
We quickly realized that in order to understand the full extent of our life,
we need to look beyond this 2% and explore the unknown.
There is more that I want to share you today.
DNA cannot only generate RNA.
So, RNA is very central part of our process,
and RNA can be considered as a cousin to our DNA.
What has been known is that RNA is required to make proteins.
But we've realized is that in this non-coding regions of our DNA,
they can also generate RNA.
But what’s unique about this, is that this RNA do not make proteins.
So, there must be something more that this protein is doing.
In order to understand this non-coding RNA,
many laboratories around the world, including ourselves,
have started to characterize them.
Let me give you a couple of examples of what non-coding RNA can actually do.
One of the things it can do is that it can act as a connector.
It can bring two proteins together to join into one simple complex.
You can imagine it like a Shinkansen train.
You have two train carriages and you need a little connector in-between
to bring these two carriages together.
Just like that, these non-coding RNAs are able to bring two proteins together.
Therefore, these proteins then can be functional inside our cells.
Another example of this non-coding RNA is that it can act as a GPS system.
This non-coding RNA contains zip code in the genetic code,
that will help its proteins to navigate inside the cells
and direct them to the place where they need to go.
These new mechanisms that we are discovering about this non-coding RNA,
is rebuilding new biology inside our cells that we didn’t know before.
And because of these pathways,
we are also figuring out new ways to find solutions for therapeutic purpose.
We are realizing these non-coding RNAs are far more than just junk,
that they are actually the control centers of our DNA,
and regulating a lot of processes that we didn’t know before.
To truly understand the blueprint of life, we have to look beyond
and start to explore more what is hidden in these regions.
Although I only highlighted two examples today,
through collective effort from our laboratory and around the world
we discovered in fact 25,000 or more of these types of non-coding RNAs.
And we only know a very small fraction
of these non-coding RNAs and their functions.
So, we are just scratching the surface of the iceberg.
In order to understand full complexity of our live,
we need to dive deep and explore this uncharted territory.
To achieve this and to understand to full characterization
of long non-coding RNA in the cells, we have started a new project.
One of the aims is to build,
to achieve this, by building a robotic system
that can perform high throughput screening.
What it does is that we are able to remove these non-coding RNAs from our cells,
one by one.
And you can use DNA sequencers to measure what are the genes
that switch on and switch off inside the cells.
Just to illustrate this idea,
imagine a car made up of multiple components.
These components can be your steering wheels,
brake pedals or nuts and bolts, that make up the car.
While the car is in motion, you start to remove one component at a time.
What will happen to a car?
Will it steer away? Would the driver feel safe?
By measuring these activities,
we can understand how important this one component can be inside the car.
So in the same token, we are using a similar approach
where we are removing one non-coding RNA at a time inside the cell,
to understand how important a particular non-coding RNA is
to the make up of the cells.
Over the past three years,
we have characterized many of these non-coding RNAs.
We are using in-depth computational analysis
to understand the complexity of the life.
But of course none of these can be achieved alone.
And this really is a big project and a whole global effort is required.
To achieve that we have started an international consortium
called "FANTOM6."
It is a consortium of scientists all around the world,
aiming to build the most comprehensive catalog
of these long non-coding RNAs.
The consortium consists of hundreds of scientists around the world,
from US, Germany, UK and Australia.
And I’ve been truly honored to co-lead this consortium
together with Drs. Piero Carninci and Michiel de Hoon
at the RIKEN Institute.
There’s a lot of activities ahead of us
and we are all thrilled to be a part of this journey.
We came a very long way from the time when we labeled these DNA :
"Junk"
But now, we are really starting to redefine the meaning of DNA.
Through discovery of new non-coding RNAs, we are entering into whole new world
that no one has gone before.
My dream is that this catalog of non-coding RNA
will be the building block that, can spiral new inspiration
and that it will help to improve our health,
and provide new solutions to cure diseases.
Thank for your attention.
(Applause)