trans

64 TRANSCRIPTION
intragenic promoter element, however, is not
present in all U snRNA genes, because, as was
recently found, A and B box elements suffice
for accurate and efficient transcription of the
putative U1 snRNA gene in T. brucei (Figure
3.3). The functional association between U
snRNA genes or the 7SL RNA gene with tRNA
genes is a common feature in trypanosomatids
(Figure 3.3) but it does not appear to be
particularly parasite-specific because B boxes
have been found to be linked with U snRNA
genes of other organisms. For example, U6
snRNA gene expression in yeast depends on a
B box which is located downstream of the U6
coding region and which, by binding the transcription
factor IIIC, is involved in remodeling
the chromatin structure. However, it seems
that the tRNA gene promoter elements of trypanosomatid
U snRNA and 7SL RNA genes
have additional functions and participate
directly in the formation of a transcription initiation
complex. In favor of this hypothesis are
the findings that the A box but not the B box is
essential for in vitro transcription of the T. brucei
U6 snRNA gene, that A and B boxes suffice
to direct accurate transcription of the T. brucei
candidate U1 snRNA gene, and that the position
of the A box is highly conserved (Figure
3.3) and cannot be changed without dramatically
affecting U snRNA gene transcription. It
is unknown how the tRNA gene promoter elements
direct transcription of the associated
small RNA gene. An attractive hypothesis states
that binding of the transcription factors to the
tRNA gene promoter elements bends the DNA
so that the DNA-protein complexes of the
A and B boxes come in contact with the transcription
initiation region of the associated
small RNA gene. In accordance with this
hypothesis, it was shown in yeast that TFIIIB,
the factor which binds to the A box, imposes
multiple bends on DNA. Similarly, specific
binding of trypanosome nuclear factors to the
internal tRNA gene promoter elements
resulted in DNA bending.
PERSPECTIVE
To the best of our knowledge, existing drugs
against parasite infection do not interfere with
gene transcription, although inhibitors such
as -amanitin, tagetitoxin, or rifampicin indicate
that this is a possibility. For the development
of potential parasite-specific transcription
inhibitors we need to overcome our limited
knowledge of transcription factors in parasites.
The prospects of learning more about
transcriptional processes is excellent. DNA
transfection technology, in vitro transcription
systems and growing genome databases of
parasitic organisms will facilitate the identification
and functional characterization of such
factors in the future. Parasite-specific mechanisms
of transcription and the evolutionary
distance between parasites and host organisms
make it likely that essential transcription
factors or factor domains exist which either
have no counterpart or may substantially
deviate from a counterpart in the host and,
therefore, may serve as suitable and specific
targets against the parasite.
FURTHER READING
Blumenthal, T. (1998). Gene clusters and polycistronic
transcription in eukaryotes. Bioessays
20, 480–487.
Borst, P. and Ulbert, S. (2001). Control of VSG gene
expression sites. Mol. Biochem. Parasitol. 114,
17–27.
Campbell, D.A., Sturm, N.R. and Yu, M.C. (2000).
Transcription of the kinetoplastid spliced leader
RNA gene. Parasitol. Today 16, 78–82.
Cross, G.A., Wirtz, L.E. and Navarro, M. (1998).
Regulation of VSG expression site transcription
MOLECULAR BIOLOGY