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

332 Chapter 6: How Cells Read the Genome: From DNA to Protein
Figure 6–46 Visualization of some prominent nuclear bodies. The
protein fibrillarin (red), a component of several snoRNPs, is present at both
nucleoli and Cajal bodies; the latter are indicated by the arrows. The Cajal
bodies (but not the nucleoli) are also highlighted by staining one of their
main components, the protein coilin; the superposition of the snoRNP and
coilin stains appears pink. Interchromatin granule clusters (green) have been
revealed by using antibodies against a protein involved in pre-mRNA splicing.
DNA is stained blue by the dye DAPI. (From J.R. Swedlow and A.I. Lamond,
Gen. Biol. 2:1–7, 2001. With permission from BioMed Central. Micrograph
courtesy of Judith Sleeman.)
disrupting a particular type of nuclear body often has little effect on cell viability.
It seems that the main function of these aggregates is to bring components
together at high concentration in order to speed up their assembly. For example,
it is estimated that assembly of the U4/U6 snRNP (see Figure 6–28) occurs ten
times more rapidly in Cajal bodies than would be the case if the same number of
components were dispersed throughout the nucleus. Consequently, Cajal bodies
appear dispensible in many types of cells but are absolutely required in situations
where cells must proliferate rapidly, such as in early vertebrate development.
Here, protein synthesis (which depends on RNA splicing) must be especially
rapid, and delays can be lethal.
Given the prominence of nuclear bodies in RNA processing, it might be
expected that pre-mRNA splicing would occur in a particular location in the
nucleus, as it requires numerous RNA and protein components. However, as we
have seen, the assembly of splicing components on pre-mRNA is co-transcriptional;
thus, splicing must occur at many locations along chromosomes. Although
a typical mammalian cell may be expressing on the order of 15,000 genes, transcription
and RNA splicing takes place in only several thousand sites in the
nucleus. These sites are highly dynamic and probably result from the association
of transcription and splicing components to create small factories, the name given
to specific aggregates containing a high local concentration of selected components
that create biochemical assembly lines (Figure 6–47). Interchromatin
MBoC6 m6.48e/6.46
10 µm
scaffold
protein
proteins aiding
transcription and
pre-mRNA processing
chromosome A
aggregation
factor
tail of RNA
polymerase
DNA
mRNA
(A)
(C)
2 µm
chromosome B
Figure 6–47 A model for an mRNA production factory. mRNA production is made more efficient in the nucleus by an aggregation of the many
components needed for transcription and pre-mRNA processing, thereby producing a specialized biochemical factory. In (A), a postulated scaffold
protein holds various components in the proximity of a transcribing RNA polymerase. Other key components are bound directly to the RNA
polymerase tail, which likewise serves as a scaffold (see Figure 6–22), but for simplicity these are not shown here. In (B), a large number of such
scaffolds have been brought together to form an aggregate that is highly enriched in the many components needed for the synthesis and processing
of pre-mRNAs. Such a scaffold model can account for the several thousand sites of active RNA transcription and processing typically observed
in the nucleus of a mammalian cell, each of which has a diameter of roughly 100nm and is estimated to contain, on average, about 10 RNA
polymerase II molecules in addition to many other proteins. MBoC6 (C) Here, n6.300/6.47 mRNA production factories and DNA replication factories have been visualized
in the same mammalian cell by briefly incorporating differently modified nucleotides into each nucleic acid and detecting the RNA and DNA produced
using antibodies, one (green) detecting the newly synthesized DNA and the other (red) detecting the newly synthesized RNA. (C, from D.G. Wansink
et al., J. Cell Sci. 107:1449–1456, 1994. With permission from The Company of Biologists.)