400
Cell Nucleus Biogenesis, Structure and Function
mRNA export is coupled to many of the
proceeding steps of gene expression. In
broad terms, the pathway that delivers
mature mRNAs to the cytoplasm is in-
fluenced by promoter strength, the RNA
polymerase complex that performs synthe-
sis, transcriptional elongation, as well as
down stream processing events such as
RNA splicing and polyadenylation. A sig-
niFcant aspect of this pathway reflects the
fact that mRNAs are retained at the tran-
scription site until the required processing
events have been performed. This is likely
to be part of the ‘‘quality control’’ process,
which ensures that only authentic mature
mRNAs are exported to the cytoplasm.
Apart from the general export factors,
many proteins have been described that
interact with different classes of RNA
to regulate RNA export. Certain factors
regulate the export of different classes of
mRNA and others are essential for the
export of ribosomes and RNA–protein
complexes that contain RNAs transcribed
by RNA pol III.
3.4.3
Nuclear Transport – Facilitated
Diffusion
We have looked in some detail at the
molecules involved in nuclear transport
without concern for the mechanisms that
drive the transport process itself. It was
noted above that the nuclear pore is
essentially ‘‘open’’ to small molecules.
Transportthatismediatedbykaryopherins
is perceived as being a form of directed
diffusion – or facilitated translocation. The
critical question to address here is how do
pores exert a high degree of selectivity on
the nuclear transport receptors while ex-
cluding proteins that do not contain the
appropriate receptor signals. A critical Frst
step requires an association – binding – of
the transport receptor to target molecules
within the pore complex. These interac-
tions have been characterized in detail.
What is not clear, however, is why this pri-
mary interaction would inevitably lead to
the cargo being directed through the pore.
Models of facilitated translocation sup-
pose that selectivity – gating – is achieved
through interactions between the trans-
port complex and particular protein motifs
inth
ep
o
r
ep
r
o
t
e
in
s–c
a
l
l
e
d
FG-repeats
.
The ±G-repeats are proposed to provide a
sort of hydrophobic plug that severely re-
duces the efFciency with which molecules
that are not destined for transport are
able to pass through nuclear pores. The
receptor/cargo complex, in contrast, by
virtue of its structure and interaction
with other pore components is able to
diffuse through this region of the pore.
Though the details by which selectivity is
achieved remain to be reFned, changes
in pore permeability following treatment
with organic solvents are consistent with
a role for a hydrophobic meshwork (pro-
vided by the ±G-repeats) inside the pore
channel.
3.5
Nuclear Architecture and Nuclear
Compartments
3.5.1
Nuclear Compartments
In mammalian cells, the nuclear mem-
brane deFnes two major cell compart-
ments – the nucleus and cytoplasm – that
have quite distinct structural character-
istics (±ig. 4). The cytoplasm gives an
impression of being highly structured with
many discrete organelles such as mito-
chondria and lysosomes and has other
regions that contain dense clusters of
ribosomes (each ribosome is 25 nm in
diameter) performing protein synthesis.
The nucleus is also structured, but the ba-
sic principles that deFne nuclear structure
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