402
Cell Nucleus Biogenesis, Structure and Function
of proliferation in cancer diagnosis. Nu-
cleoli range in size from 0.5 to 5
.
0
µ
m
and are assembled around the active ri-
bosomal RNA genes. Each diploid human
cell has about 300 copies of the ribosomal
RNA locus. Each locus contains a single
transcription unit of 13.3 kb, which is pro-
cessed posttranscriptionally to generate 3
RNA molecules – the 28S, 18S and 5.8S
(in vertebrates) rRNAs – which, together
with 5S RNA are the structural RNAs that
dictate ribosome assembly and function.
The genes are located on 5 human chro-
mosomes at the subtelomeric regions of
c13, 14, 15, 21, and 22, where they are
found in short tandem arrays – typically
as clusters of 3 to 5 rDNA repeats. In
most proliferating human cells, only about
one-third of the total cell complement of
ribosomal genes is active at any time. In
proliferating cells, nucleoli form as riboso-
mal RNA synthesis is reestablished, soon
after cell division is complete. Ribosomal
RNA genes retain associated transcription
factors throughout mitosis and these pro-
vide efFcient targets for the assembly of
transcription complexes at the onset of
interphase. As transcription recovers, the
components involved are believed to in-
teract to form the characteristic nucleolar
morphology. Each active center is deFned
by a Fbrillar center (±C) that has a distinct
Fbrogranular appearance and is rich in
the machinery that is required to generate
rRNA. The surface of each ±C is coated
with a much denser dense Fbrillar com-
ponent (D±C) that contains the nascent
transcripts and their associated proteins.
The transcribed rRNA genes lie along the
interface of the ±C and D±C and a sin-
gle ±C will typically have 3 to 5 associated
active genes.
Ribosomal RNA genes are the most
active transcription units in mammalian
cells. It takes about 3 min to complete syn-
thesis of the primary transcript, and poly-
merases are engaged onto the promoter
with such efFciency that each active gene
has 100 to 120 engaged RNA polymerase I
complexes. In order to achieve this level of
synthesis, new initiation events must oc-
cur at roughly 1.5-s intervals; the residence
time of the major transcription factors in
the ±C is
5s and the residence time
for RNA polymerase I on the promoter is
roughly 1 s. The primary transcripts are
processed to generate mature ribosomal
RNAs. This is an extremely complex pro-
cess that involves a number of speciFc
cleavage events and RNA modiFcations,
typically methylation. These posttranscrip-
tional events are directed by at least 100
special small nucleolar RNA–protein com-
plexes (snoRNPs). The mature rRNAs then
associate with the requisite ribosomal pro-
teins and begin their passage from the
synthetic center to the cytoplasm. ±or
the early stages–about 1h–of this mi-
gration they remain nuclear and occupy
the nucleolar granular component (GC), a
morphologically punctate or granular zone
that surrounds the active rRNA transcrip-
tion centers. Eventually, the mature 40 and
60S ribosomal particles pass from the nu-
cleolus and through the nucleoplasm to
the nuclear periphery from where they exit
the nucleus through nuclear pores.
3.5.3
Nuclear Bodies and Domains
Other nuclear structures have been de-
scribed as nuclear bodies and domains.
Many cell types have a small number
(typically 1–5) of coiled or Cajal bodies,
which are generally spherical, measure 0.3
to 1
µ
m across and in cross-section, ap-
pear as a network of coiled Fbers. Coiled
bodies are found in both animals and
plants and contain many different pro-
teins, including p80 coilin (the diagnostic
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