Page 23 - Color_Atlas_of_Physiology_5th_Ed._-_A._Despopoulos_2003

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primary mRNA strand by splicing (! C1b, D) brane of the endoplasmic reticulum (ER),
and then degraded. The introns, themselves, which is described below (! F).
contain the information on the exact splicing The mRNA exported from the nucleus
site. Splicing is ATP-dependent and requires travels to the ribosomes (! C1), which either
the interaction of a number of proteins within float freely in the cytosol or are bound to the
a ribonucleoprotein complex called the cytosolic side of the endoplasmic reticulum, as
spliceosome. Introns usually make up the lion’s described below. Each ribosome is made up of
share of pre-mRNA molecules. For example, dozens of proteins associated with a number
they make up 95% of the nucleotide chain of
of structural RNA molecules called ribosomal
Fundamentals and Cell Physiology posttranscriptional modification. complexes genes in the nucleolus, then separately exit the
coagulation factor VIII, which contains 25 in-
RNA (rRNA). The two subunits of the ribosome
trons. mRNA can also be modified (e.g.,
are first transcribed from numerous rRNA
through methylation) during the course of
cell nucleus through the nuclear pores. As-
RNA now exits the nucleus through nuc-
sembled together to form a ribosome, they
now comprise the biochemical “machinery”
lear pores (around 4000 per nucleus) and en-
for protein synthesis (translation) (! C2). Syn-
ters the cytosol (! C1c). Nuclear pores are
high-molecular-weight
thesis of a peptide chain also requires the pres-
protein
ence of specific tRNA molecules (at least one
(125 MDa) located within the nuclear en-
velope. They allow large molecules such as
for each of the 21 proteinogenous amino
transcription factors, RNA polymerases or cy-
bound to the C–C–A end of the tRNA molecule
toplasmic steroid hormone receptors to pass
(same in all tRNAs), and the corresponding an-
1 into the nucleus, nuclear molecules such as acids). In this case, the target amino acid is
ticodon that recognizes the mRNA codon is lo-
mRNA and tRNA to pass out of the nucleus, and
other molecules such as ribosomal proteins to cated at the other end (! E). Each ribosome
travel both ways. The (ATP-dependent) pas- has two tRNA binding sites: one for the last in-
sage of a molecule in either direction cannot corporated amino acid and another for the one
occur without the help of a specific signal that beside it (not shown in E). Protein synthesis
guides the molecule into the pore. The above- begins when the start codon is read and ends
mentioned 5! cap is responsible for the exit of once the stop codon has been reached. The ri-
mRNA from the nucleus, and one or two bosome then breaks down into its two sub-
specific sequences of a few (mostly cationic) units and releases the mRNA (! C2). Ribo-
amino acids are required as the signal for the somes can add approximately 10–20 amino
entry of proteins into the nucleus. These acids per second. However, since an mRNA
sequences form part of the peptide chain of strand is usually translated simultaneously by
such nuclear proteins and probably create a many ribosomes (polyribosomes or polysomes)
peptide loop on the protein’s surface. In the at different sites, a protein is synthesized much
case of the cytoplasmic receptor for glucocor- faster than its mRNA. In the bone marrow, for
ticoids (! p. 278), the nuclear localization sig- example, a total of around 5 ! 10 hemoglobin
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nal is masked by a chaperone protein (heat copies containing 574 amino acids each are
shock protein 90, hsp90) in the absence of the produced per second.
glucocorticoid, and is released only after the The endoplasmic reticulum (ER, ! C, F)
hormone binds, thereby freeing hsp90 from plays a central role in the synthesis of proteins
the receptor. The “activated” receptor then and lipids; it also serves as an intracellular Ca 2+
reaches the cell nucleus, where it binds to store (! p. 17 A). The ER consists of a net-like
specific DNA sequences and controls specific system of interconnected branched channels
genes. and flat cavities bounded by a membrane. The
The nuclear envelope consists of two mem- enclosed spaces (cisterns) make up around 10%
branes (= two phospholipid bilayers) that of the cell volume, and the membrane com-
merge at the nuclear pores. The two mem- prises up to 70% of the membrane mass of a
branes consist of different materials. The ex- cell. Ribosomes can attach to the cytosolic sur-
10 ternal membrane is continuous with the mem- face of parts of the ER, forming a rough endo-
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Despopoulos, Color Atlas of Physiology © 2003 Thieme
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