Documente Academic
Documente Profesional
Documente Cultură
1: Activation (overview),
Transcription, Translation.
Review
An active gene is one that is being
transcribed, and whose transcription product
is being translated, and whose translation
product affects cellular behavior/development.
Genes are activated by transcription factors
the principal way transcription is controlled
Transcription factors are proteins that
themselves are gene products.
Transcription factors often require a cofactor,
a very important environmental signal.
Translation Product:
(Active Protein)
Change in
Change in
transcription factor
cofactor level
activity
Transcription
A good reference:
(Blackwell, 2001)
The
transcription
bubble,
White, Fig.
1.8
for translation
1 sec-1
10 min -1
Transcription
2500 nt min-1
3,000 nt min-1
RNA processing
not applicable
ca. 10 min
ca. 10 min
Nucleocytoplasmic
transport
not applicable
ca. 10 min
Half-life, mRNA
1-3 min
1-20 h
mRNA translation
2700 nt min-1
720 nt min-1
Half-life, protein
20-60 min
2-100 h
RNA polymerase
Ribosome
Critical Factors:
For transcription the attachment rate,
since the number of gene copies (one or
two), transcription velocity and length are
fixed.
For translation the number of mRNA's
present, since the ribosomal attachement
rate, translation velocity and length are
fixed.
Transcription Factors
It is important to remember that transcription factors are
proteins, come from genes (like all proteins), and may influence
either their predecessor gene or often other genes.
Summary of the structure of
the Engrailed homeodomain
bound to DNA, as revealed by
X-ray crystallography.
Cylinders represent the three
-helices of the homeodomain,
ribbons represent the sugar
phosphate backbone of the
DNA and bars symbolize the
base pairs. The recognition
helix (3) is shown in red.
Transcription
factors have
many shapes
and thus modes
of interaction
with DNA
Basal Transcription
Factors
TATA box TATAa/tAa/ t
Initiator YYANa/ tYY,
where Y is a pyrimidine, N
is any base, and
transcription begins at the
A
Picture shows assembly
of basal pol II on
adenovirus ML promoter
Transcription
Control by
Stimulated
Translocation
Myogenesis
Upstream regulators force
differentiation to
mesodermal precursor
cells that then express
bHLH proteins that
stimulate transcription of
their own genes. They also
activate genes that make
MEF2, which further
accelerates transcription of
genes for bHLH proteins.
MEF2 and bHLH proteins
both stimulate other
muscle-specific genes.
Positive feedback!
Transcription factors
determine mRNA production;
do they determine mRNA
number?
(mRNA number is what
determines translation)
d (mRNA)
Production rate k (mRNA)
dt
This is the first part of the Goodwin equation set.
Frequently a translation
product will mediate the level
of another metabolite
(galactosidase, tryp enzymes)
This can give rise to a third set of
Goodwin equations.
Product levels determined by the third set
often provide the "loop-closing" feedback.
Translation Product:
(Active Protein)
Change in
Change in
transcription factor
cofactor level
activity