Alternative Splicing
More than 5% of all genes can
produce variant proteins by alternative splicing. The
protein variants made by alternative
splicing can have
important functional differences. The protein
variants may differ in the presence or absence of
structural or functional domains. In some cases one
splicing pathway
can lead to a translatable mRNA, while the
alternative
splicing pathway
results in a non-translatable mRNA.
Biologically important processes involve alternative
splicing. The determination of sexes in Drosophila is
for example partly determined at the level of
alternative splicing. Many cell types in the human
body express different versions of proteins because
of alternative spicing. For example, the three
different types of muscle cells in the human body
make three different versions of the protein
tropomyosin by alternative splicing.
Many principle variants of alternative
splicing have been
described. (see illustration) A
pre-mRNA can for
example contain two alternative 5' (or 3')
exon-intron borders, which can be used to excise a
shorter or longer version of an intron. Pre-mRNAs
which contain more than two introns can also be
spliced to include all exons in the mRNA, or to
exclude one or several of the exons. The regulation
of alternative
splicing is not yet
well known. In some cases, a specific protein is
present that binds to one 3' splice site of an
intron and hides it
from the
splicing factors.
This leads to the usage of the alternative 3' splice
site instead. In other cases, one of two alternative
5' splice sites is weaker than the other and much
less often used. The usage of the weak splice site
can be stimulated by the binding of SR proteins to an
RNA sequence
located close to the 5' splice site, thereby helping
the
splicing factors to
find the weak 5' splice site.
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