Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

330 Chapter 6: How Cells Read the Genome: From DNA to Protein
Figure 6–43 Changes in the appearance of the nucleolus in a human cell
during the cell cycle. Only the cell nucleus is represented in this diagram. In
most eukaryotic cells, the nuclear envelope breaks down during mitosis, as
indicated by the dashed circles.
nuclear
envelope
of macromolecules, including the rRNA genes themselves, precursor rRNAs,
mature rRNAs, rRNA-processing enzymes, snoRNPs, a large set of assembly factors
(including ATPases, GTPases, protein kinases, and RNA helicases), ribosomal
proteins, and partly assembled ribosomes. The close association of all these components
allows the assembly of ribosomes to occur rapidly and smoothly.
Various types of RNA molecules play a central part in the chemistry and structure
of the nucleolus, suggesting that it may have evolved from an ancient structure
present in cells dominated by RNA catalysis. In present-day cells, the rRNA
genes have an important role in forming the nucleolus. In a diploid human cell,
the rRNA genes are distributed into 10 clusters, located near the tips of five different
chromosome pairs (see Figure 4–11). During interphase, these 10 chromosomes
contribute DNA loops (containing the rRNA genes) to the nucleolus; in
M phase, when the chromosomes condense, the nucleolus fragments and then
disappears. Then, in the telophase part of mitosis, as chromosomes return to
their semi-dispersed state, the tips of the 10 chromosomes reform small nucleoli,
which progressively coalesce into a single nucleolus (Figure 6–43 and Figure
6–44). As might be expected, the size of the nucleolus reflects the number of ribosomes
that the cell is producing. Its size therefore varies greatly in different cells
and can change in a single cell, occupying 25% of the total nuclear volume in cells
that are making unusually large amounts of protein.
Ribosome assembly is a complex process, the most important features of which
are outlined in Figure 6–45. In addition to its central role in ribosome biogenesis,
the nucleolus is the site where other noncoding RNAs are produced and other
RNA–protein complexes are assembled. For example, the U6 snRNP, which functions
in pre-mRNA splicing (see Figure 6–28), is composed of one RNA molecule
and at least seven proteins. The U6 snRNA is chemically modified by snoRNAs in
the nucleolus before its final assembly there into the U6 snRNP. Other important
RNA–protein complexes, including telomerase (encountered in Chapter 5) and the
signal-recognition particle (which we discuss in Chapter 12), are assembled at the
nucleolus. Finally, the tRNAs (transfer RNAs) that carry the amino acids for protein
synthesis are processed there as well; like the rRNA genes, the genes encoding
tRNAs are clustered in the nucleolus. Thus, the nucleolus can be thought of as a
large factory at which different noncoding RNAs are transcribed, processed, and
assembled with proteins to form a large variety of ribonucleoprotein complexes.
nucleolus
nucleolar
dissociation
nucleolar
association
G 2
MITOSIS
G 1
preparation
for mitosis
prophase
metaphase
anaphase
telophase
preparation
for DNA
replication
S
DNA
replication
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10 µm
Figure 6–44 Nucleolar fusion. These light micrographs of human fibroblasts grown in culture show
various stages of nucleolar fusion. After mitosis, each of the 10 human chromosomes that carry a
cluster of rRNA genes begins to form a tiny nucleolus, but these rapidly coalesce as they grow to
form the single large nucleolus typical of many interphase cells. (Courtesy of E.G. Jordan and
J. McGovern.)
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