Biology Reference
In-Depth Information
1. EVOLUTION OF EUKARYOTIC SPLICING MACHINES
The continuity of the information content of modern eukaryotic
genes is frequently interrupted by the presence of intervening sequences,
or introns, which must be accurately removed or “spliced” out from primary
transcripts before they can be used by the cell. In addition, introns them-
selves often harbor regulatory or otherwise functional sequences, and thus
their timely removal is essential for their cellular function. The intronic
sequences, especially in higher eukaryotes, are typically much longer than
the non-intronic sequences called exons, and the sequence elements that
specify the intron-exon boundaries are highly complex. Thus, the accurate
separation of these two sets of functional sequences that coexist in eukaryotic
primary transcripts poses a challenge to eukaryotic gene expression machin-
ery. The modern mammalians have one of the most complex splicing pat-
terns among extant eukaryotes. However, it is likely that even in primordial
eukaryotes, splicing was already a highly challenging task.
Based on currently accepted models of eukaryotic evolution, introns
likely originated from self-splicing ribozymes that dated from precellular life
and constituted the majority of the genomes of ancient eukaryotes.
1
As
removal of this large fraction of intronic sequences was necessary for the sur-
vival of ancient eukaryotes, an elaborate cellular machine dedicated to
removal of the introns, called the spliceosome, was already present in the
last common eukaryotic ancestor.
2
Current data from phylogenetic studies
indicate that ancient spliceosomes were highly similar to their modern coun-
terparts, with the majority of spliceosomal components already in place.
2,3
As can be expected from their highly critical function, spliceosomes are very
complex cellular machines. They consist of five RNAmolecules named U1,
U2, U4, U5, and U6 small nuclear RNA (snRNA), and from 60 to 150 dif-
ferent proteins depending on the species.
4,5
Although the origin and evolu-
tion of early spliceosomes is still largely mysterious, several lines of evidence
suggest that eukaryotic spliceosomes have likely evolved from self-splicing
introns.
6-11
This hypothesis is partly based on the fact that the mechanism of
intron removal by the spliceosome, which is performed through two con-
secutive transesterification reactions resulting in the removal of a branched
lariat intron, is identical to the splicing reaction performed by a class of extant
self-splicing introns called group II introns.
12-16
Interestingly, the RNA
components of the spliceosome, the snRNAs, show unmistakable similari-
ties to fragments of the catalytically essential domains of group II introns in
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