trans

POST-TRANSCRIPTIONAL REGULATION IN EUKARYOTIC MODEL SYSTEMS 69
a gene with several introns may be the template
for a variety of mRNAs, generated by alternative
splicing and encoding proteins which
can have quite divergent functions. Aberrantly
processed mRNAs, or mRNAs containing transcription
errors, need to be eliminated before
they can be translated into erroneous proteins.
Some RNAs can perform their function
correctly only if they are tightly localized to
one part of the cell. Some proteins are needed
only transiently, so that their synthesis must
be abruptly halted by destruction of the corresponding
mRNA. And some proteins need
to be synthesized de novo even when no RNA
synthesis is taking place. In prokaryotes also,
different RNAs have different stabilities and
some are translated more efficiently than
others. At present, very little is known about this
aspect of regulation in parasites. The only family
in which it has been studied in any detail is the
kinetoplastids – for the very good reason that
these organisms can’t control transcription
of the vast majority of their genes. If all genes
are being transcribed all the time, something
has to be done to preserve the RNAs that are
needed, and eliminate the rest. This chapter
will first summarize what is known about posttranscriptional
regulation in eukaryotic model
systems. Next it will describe in detail the available
information about the kinetoplastids,
before mentioning other parasites.
POST-TRANSCRIPTIONAL
REGULATION IN
EUKARYOTIC MODEL
SYSTEMS
RNA processing
With the recent publication of the draft human
genome, it has become clear that the number
of predicted genes alone does not correlate at
all with the complexity of the organism. Thus
the predicted number of genes in man is only
around 30 000, as against an estimated 19 000 in
the worm Caenorhabditis elegans and 6200 in
the yeast Saccharomyces cerevisiae. The coding
capacity of the genome of a multicellular
organism is much higher than the predicted
gene number because genes are split into
multiple exons. Transcription can start and
stop in different places, and the exons can be
spliced in a variety of combinations to give
different mRNAs and proteins. The pattern of
splicing can vary during development and can
determine the fate, not just of individual cells
but of the whole organism. For example, sex
determination in Drosophila is dependent on
alternative splicing. In addition, the position
of polyadenylation can influence the function
of the encoded protein. A classic example here
is the exclusion or inclusion of the membrane
anchors of immunoglobulins; if the portion of
the gene encoding the anchor is chopped off by
use of an alternative polyadenylation site, the
immunoglobulin is secreted.
Some RNAs in mammalian cells are subject
to another form of post-transcriptional modification:
editing by enzymatic modification of
individual bases. This process, which is entirely
different from the editing seen in kinetoplastid
mitochondria, is for example important in
determining the properties of some receptors
in the brain.
Any of these processes could be important
in parasite gene regulation, but until now there
are no published examples.
Export from the nucleus and
localization
Once an mRNA has been correctly processed,
it is escorted to the cytosol by proteins. Crucial
to this export is the presence of a 5-cap structure,
which is made of modified bases and is
MOLECULAR BIOLOGY