Before computers and digital cameras, movies were edited hand.
Editors would get rolls of raw film and physically cut and paste the scenes together.
This process was called SPLICING. But what does this
old editing technique have to do with human disease? "It runs in the family."
Chances are, you've heard this phrase before.
Today, we know that the 'biological details of our bodies'
passed down from our parents. This includes physical traits,
like your hair color, or height, but also your susceptibility to certain kinds
of disease.
All this information encoded
in your DNA. DNA is made up
four nucleotide bases, A, G, C
and T that spell out the information required for a human cell to carry out the
various functions of like
These are organized into units called genes.
Now, every cell in your body contains workers called ribosomes.
Ribosomes build proteins, and each protein carries out a specific task in the
cell.
However, ribosomes need instructions every time they put together a protein.
inside every cell there is a nucleus, and inside every nucleus,
there is a copy of your DNA. Think of the nucleus as a media center.
It produces tutorials that teach ribosomes how to build proteins,
and right now, we need to build a protein to strengthen the walls in the nucleus.
We'll call it Protein X.
Imagine your DNA is like a strip of film.
From here to hear is one gene.
Inside this gene is the whole tutorial for building protein X.
how do we make the tutorial? First,
the nucleus copies this gene.
This copy is called pre-mRNA, and can be edited.
The original DNA is
preserved for future reference. But the tutorial is not edited yet,
and the footage is separate.
Part of it is here, another part is here,
another part is here. These frames with footage
are called exons. The film strip
also contains frames that aren't parted of the video.
The sequences are called introns and will not be in the final tutorial.
One of their purposes is to provide instructions on how
and where to edit the film. This
is the spliceosome.
Think pf it as a film editor. It follows directions in
introns, cuts them out, and paste the exon's together.
This entire process is known splicing.
Now we have a coherent tutorial video that can be relayed to the ribosomes.
Splicing is crucial to the correct construction of proteins.
Unfortunately, mistakes can occur
as a result of mutations. Mutations are variations from the nucleotide sequences
in our original DNA. We used to think
only mutations in the movie frames themselves caused disease.
But now, we know that mutations that affect the splicing process
can also cause disease! Back to protein X.
If there are no mutations in the film, Protein X will look like this,
and fit perfectly into the cell wall. But let's say there is a mutation in the film
frames.
This might cause Protein X to have a little hole in it, like this.
When it slots in, it leaves a gap in the wall,
and you get a slightly weaker structure.
Now, let's say there's a splicing mutation: a mutation in instructional frames.
This will cause the organization, rather than the content of the video to be altered.
some scenes might be missing, others might be cut short,
and others may include unnecessary segments of film.
This will have a much bigger effect on how Protein X is built.
The finished protein might have an entire region missing, like this.
And this is happening in many cells at once,
so imagine the kinds of damage that spicing mutations can do.
so why is spicing important? Experts estimate that one third of
all heritable diseases involves an error in spicing.
Still, we don't have a detailed understanding of how exactly spicing
goes wrong.
Part of the problem is that each person has about 3 million unique
differences in their DNA, so it's hard to tell which ones cause disease.
Today, researchers are using computers
and statistics to comb through mountains of mutations
and model their effect on splicing. We hope to find patterns that tell us how
splicing is directed.
Eventually, doctors may be able to come up with personalized treatments,
by studying the mutations that affect how our genetic tutorials
are edited