Cell Nucleus Biogenesis, Structure and Function
383
activated at the corresponding promoter.
An excellent example of this is provided by
enhancer elements within the mammalian
β
-globinlocuscontrolregion(LCR),which
are located about 50 kbp from the gene pro-
moters in this locus that are activated at
different times of development.
Particular features of the transcription
factor proteins generate binding speci-
Fcity. Many classes of transcription factor
have been described, but the majority of
factors fall into three main groups with
(1) helix–turn–helix motifs; (2) zinc Fn-
gers; (3) leucine zippers.
The homeodomain of vertebrate hox
genes
is
a
classical
example
of
the
helix–turn-helix transcription factor motif.
The homeodomain is composed of 60
amino acids that fold as three helices.
Helices 2 and 3 form the helix–turn–helix
motif and helix 3 interacts with the major
groove of DNA.
Though variants have been described,
the characteristic feature of the zinc Fnger
motif is a zinc atom associated with two
cysteine and two histidine residues. The
human Gli protein is a good example
that is involved in bone development and
also ampliFed in some human tumors.
The factor contains Fve zinc Fngers, of
which four interacts with each of the
major grooves of DNA where they wrap
around the DNA for a full helical turn.
Extensive contacts between the amino
acids of these structures and the bases
and phosphate residues in DNA together
generate speciFcity of factor binding.
The human oncogenes
Fos
and
Jun
are
members of the family of transcription
factors that bind to AP-1 sites within
promoters.
Fos
and
Jun
are able to form
heterodimers by virtue of the precise
spacing of hydrophobic leucine residues
in the domains of the two monomers
that provide a surface for interaction – the
leucine zipper. The alpha helices within
the monomers ‘‘zip’’ together to create a
coiled coil and a proximal basic region that
is generated in the dimer to provide a DNA-
binding domain. This basic region has
two lysine/arginine-rich regions separated
by an invariant asparagine that together
generate an interaction with the major
groove of the DNA.
2.1.3
Posttranscriptional Events – RNA
Processing
In eukaryotes, the primary transcripts of
protein coding genes must be processed
beforethematuremessengerRNAs(mR
-
NAs) are able to pass to the cytoplasm. The
processing steps include the following:
1. Addition of a 5
0
cap structure – this oc-
curs cotranscriptionally and serves a
role in RNA structure and stability. ±or-
mation of the RNA cap involves the
addition of 7-methyl guanylic acid to
the 5
0
triphosphate of the nascent tran-
script, in a reaction that involves the
two triphosphate moieties. During this
three-step reaction, the
γ
-phosphate
of
the
RNA
is
Frst
removed
by
RNA triphosphatase, GTP-RNA guanyl-
transferase then adds GMP to the
new terminal and Fnally the methyl
group is added by RNA-guanine-7-
methyltransferase. The cap may be
further modiFed by the addition of
2–O-methyl groups to the Frst or
Frst and second ribose residues of
the transcript.
2. The protein coding sequences of many
eukaryotic genes are interspersed with
noncoding introns, which must be re-
moved in order to generate mature
mRNA. This process, called
RNA splic-
ing
, begins at the time of transcription
and is completed posttranscriptionally,
at the transcription site. Splicing is
previous page 1057 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online next page 1059 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online Home Toggle text on/off