SPLICING

Definition: In molecular biology and genetics, splicing is a modification of

an RNA after transcription, in which introns are removed and exons are joined. This is
needed for the typical eukaryotic messenger RNA before it can be used to produce a
correct protein through translation.

In prokariotic cells, between the transcripted gene, the mRNA and the protein specified
by that gene there is a relation of colinearity, the succesion of the nucleotidic triplets in the gene
corresponding exactly to the succession of the aminoacids in the coded protein. However, in
eukariotic cells, the intranuclear mRNA resulting from the transcription process is much longer
than the intracitoplasmatic mRNA. This idea was first based on the observation that the DNA
which corresponds to the intranuclear mRNA containing the information for ovalbumine
sinthesis also includes fragments not found in the intracitoplasmatic mRNA. The conclusion is
that the base sequences coding ovalbumine are placed discontinualy in the genome.The genes
that code polipeptides, called exons (expressed regions), are interrupted by sequences of genes
that will not be translated called introns (intervening sequences). The gene-protein colinearity
dogma of prokariotic cells does not apply to eukariotic cells. The gene is not a structural
correspondent of the mRNA to be translated because it is a lot longer than necessary to code a
certain poplipeptide. The mRNA resulting from the transcription of the DNA also called primary
transcript or precursor mRNA (biologically inactive) is processed in order to obtain mRNAs of
different dimensions (depending on the stage of the process) or heterogenous nuclear RNA. The
final product is a mature mRNA that will serve as template for the sintesis of one or more
polipeptides. This modification of the RNA after transcription is called splicing. Practically, the
introns are discarded and the exons are joined together. RNA splicing occurs within the nucleus
before the RNA migrates to the cytoplasm.
The detailed splicing mechanism is quite complicated. There are several types of splicing
which occur in nature and each type depends on the struture of the spliced intron and the
catalysts required for splicing to occur. In eukariotic protein-coded genes most often reside
spliceosomal introns. The spliceosome, a large RNA-protein complex composed of five small
nuclear ribonucleoproteins (snRNPs, pronounced 'snurps' ), has to recognize the base sequences
in the intron-exon junction, to assure a correct juxtaposition of two exons and to execute a
catalytic act.
RNA splicing is not merely a curiosity. Approximately 15% of all genetic diseases are
caused by mutations that affect RNA splicing. Common errors include:
• Mutation of a splice site resulting in loss of function of that site. Results in exposure of a
premature stop codon, loss of an exon, or inclusion of an intron.
• Mutation of a splice site reducing specificity. May result in variation in the splice
location, causing insertion or deletion of amino acids, or most likely, a disruption of
the reading frame.
• Displacement of a splice site, leading to inclusion or exclusion of more RNA than
expected, resulting in longer or shorter exons.
 Morever, the same pre-mRNA can be spliced differently in various cell types, at different
stages of development, or in response to other biological signals. In addition, individual bases in
some pre-mRNA molecules are changed, in a process called RNA editing. One of the biggest
surprises of the sequencing of the human genome was that only approximately 40,000 genes
were identified compared with previous estimates of 100,000 or more. The ability of one gene to
encode more than one distinct mRNA and, hence, more than one protein, may play a key role in
expanding the repertoire of our genomes.