trans

RNA EDITING 37
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AAAA...
AAAA...
AAAA...
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FIGURE 2.5 Processing of multicistronic transcription units in trypanosomatids. mRNA coding regions are
boxed; 5 end maturation involves trans-splicing, 3 end maturation involves cleavage and polyadenylation.
region in a polycistronic transcript, it is necessary
to provide a discrete 5 end with a cap
and a 3 end. It is now clear that trans-splicing
serves the 5 end maturation function in trypanosomes,
i.e. addition of the spliced leader
provides both a cap and a 5 end; 3 end maturation
is achieved via endonucleolytic cleavage
and polyadenylation (Figure 2.5). Therefore,
trans-splicing is required in trypanosomes
because of the unusual mode by which genes
are transcribed in these organisms. Although
it is possible that trans-splicing serves additional
functions (e.g. in mRNA transport from
the nucleus, or stability), there is no experimental
evidence for such roles.
What is the biological function of transsplicing
in organisms other than trypanosomes?
We know that multicistronic transcription units
exist in nematodes (C. elegans in particular)
and that trans-splicing serves to process these
units. Accordingly, it is tempting to speculate
that this is the ‘universal’ function of transsplicing.
However, many more mRNAs are
trans-spliced in nematodes than are present
as part of polygenic transcripts. Therefore,
it seems likely that trans-splicing is necessary
for something else. What that is awaits further
investigation. It is clear the trans-splicing
is not used as a regulatory mechanism, nor
do trans-spliced mRNAs fall into specific
functional classes.
In summary, with the exception of trypanosomes,
the biological function(s) of transsplicing
remain largely unclear. Elucidation
of the role(s) of this unusual RNA processing
reaction will undoubtedly provide insight into
the evolutionary pressures which have caused
it to be retained in multiple phylogenetic
groups.
RNA EDITING
Discovery of RNA editing
The kinetoplast, the single mitochondrion of
kinetoplastid protozoa, has a highly unusual
gene organization, even by mitochondrial standards.
Kinetoplastid DNA is composed of
a concatenated network of roughly 20–50 large
and 5000–10 000 small circular DNAs. The
larger, ‘maxicircle’ DNAs, which range in size
from 20–39 kb in different species, contain
large regions of homology to other mitochondrial
genomes, but initially no function could
be ascribed to the 0.8–2.5 kb ‘minicircles’, even
though both types of DNAs were known to be
transcribed.
MOLECULAR BIOLOGY