What is RNA splicing

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What is RNA splicing?
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Genetic information is transferred from genes to
the proteins they encode via a messenger RNA
intermediate
DNA
GENE
3
Some genes have their protein-coding information
interrupted by non-coding sequences called
introns. The coding sequences are then called
exons
exon 1
exon 2
intron
DNA
GE
NE
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Thus expression of a gene with an intron requires
an extra step to remove the intron
exon 1
exon 2
intron
DNA
GE
NE
intron
pre-mRNA
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RNA is produced in the nucleus of the cell. The
mRNA has to be transported to the cytoplasm to
produce proteins
Ribosomes are RNA-protein machines that make
proteins, translating the coding information in
the mRNA
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Pre-messenger RNA Processing
exon
exon
intron
pre-mRNA
AAAAAAA200
M7G
cap
poly(A) tail
nucleus
cytoplasm
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In humans, many genes contain multiple introns
intron 2
intron 3
intron 4
intron 1
4
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Usually all introns must be removed before the
mRNA can be translated to produce protein
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However, multiple introns may be spliced
differently in different circumstances, for
example in different tissues.
2
4
Thus one gene can encode more than one protein.
The proteins are similar but not identical and
may have distinct properties. This is important
in complex organisms
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The possibility also exists the splicing of
mutiple introns follows alternative aberrant
pathways leading to many human pathologies
Genetic diseases
?-thalassemia, cystic fibrosis, Myotonic
dystrophy, Duschenne Muscular Distrophy, Leigh
and Hutchinson-Gilford syndrome, Retinitis
pigmentosa,
Neurological disorders
Alzheimer disease
Cancer
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Splicing a pre-mRNA involves two reactions
intron branchpoint
pre-mRNA
A
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Splicing occurs in a spliceosome an
RNA-protein complex(simplified)
spliceosome
(100 proteins 5 small RNAs)
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We are trying to understand how spliceosomes work
and how RNA splicing is regulated
Splicing works similarly in different organisms,
for example in yeast, flies, worms, plants and
animals.
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The spliceosome is only one of many RNA-proteins
machines in the cell
We are studying how RNAs and proteins interact in
order to understand how these machines work in
general and, in particular, how RNA splicing is
regulated as it affects which proteins are
produced in each cell and tissue in the body.
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Understanding these steps will be essential to
develop adapted strategies to correct aberrant
splicing in human pathologies