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Sleeping Sickness II
Sleeping Sickness and
Trypanosomes I
Why is African
trypanosomiasis such a
deadly disease?
Important pathways
discovered along the way
to understand this problem:
trans splicing and GPI
anchors
The nuts & bolts of
trypanosme gene
expression control
Why is trypanosomiasis
so deadly?
http://www.mushroomexpert.com
VSG is transcribed by Pol I
a-amanitin is a specific and highly
tubulin potent RNA polymerase inhibitor
Cells have specialized RNA
rRNA VSG polymerases to transcribe different
genes
In most cells mRNA which encodes
proteins is transcribed by the RNA
polymerase Pol2 (this enzyme can be
inhibited by the toxin a amanitin)
Ribosomal RNA is generally
transcribed by Pol1 (which is resistant
Drug to the toxin)
VSG transcription is insensitive to a-
amanitin suggesting it is transcribed by
the highly processive Pol I (however all
other mRNAs for proteins seem to be
made using Pol II as everywhere else)
How could this help to explain allelic
exclusion?
African trypansome cellular
architecture
Nucleus
Nucleoulus
Kinetoplast
How is a single expression
site activated?
Location, location,
Pol I location
PolI is found in two
spots in blood stream
DNA forms: the nucleolus
(where rRNA is
made) and a second
Nature 414:759-63
insect mammal
How is a single expression
site activated?
Nature 414:759-63
active VSG
inactive VSG
Nature 414:759-63