Can RNA Splicing Errors Cause Disease?

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


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