Page 67 - Academic Press Encyclopedia of Physical Science and Technology 3rd Molecular Biology

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Encyclopedia of Physical Science and Technology EN006H-655 June 29, 2001 21:21

516 Gene Expression, Regulation of

FIGURE 14 Editing of the Apo-B mRNA in intestinal cells. A CAA codon is edited to a UAA translational stop signal
resulting in the production of a shorter protein (Apo-B48) corresponding to the amino-terminal half of the Apo-B100
protein expressed in liver cells.

deposits them at the polyadenylation signal used for 3 In nuclear genes RNA editing appears to be rare. Also,
end formation. Even more surprising, evidence has been editing in such genes is restricted to modification of single
presented suggesting that the composition of a promoter nucleotides. In contrast, RNA editing in genes expressed
may specify alternative RNA splicing. Thus, the same in the mitochondria of protozoa, plants, and chloroplasts
gene under the transcriptional control of different pro- results in a more dramatic change of the mRNA sequence.
moters produces different types of alternatively spliced Thus, a precursor-RNA may be edited such that more than
mRNAs. This finding suggests that enhancer binding tran- 50% of the sequence in the mature mRNA is altered com-
scription factors, in addition to stimulating recruitment of pared to the primary transcription product.
the RNA polymerase to the promoter, also may partake Gene expression is also regulated at other levels, such as
in the recruitment of selective RNA processing factors to nuclear to cytoplasmic transport of mRNA, translational
the CTD tail. The future will tell whether alternative RNA efficiency of mRNA, RNA and protein stability, or protein
splicing is regulated already at the level of transcription modification. As is the case for transcriptional regulation,
initiation. control of gene expression at the level of translation often
occurs at the initiation step of the decoding process. Thus,
not all mRNAs that reach the cytoplasm are used directly
E. Other Mechanisms of Posttranscriptional
to synthesize protein. In fact, as much as 10% of genes in a
Regulation
eukaryotic cell may be regulated at the level of translation.
Although this review has focused on control of gene ex-
pression at the level of synthesis and processing of mRNA,
thereareadditionalmechanismsthatmakesignificantcon-
SEE ALSO THE FOLLOWING ARTICLES
tributions to gene expression. For example, a few genes
in vertebrates have been shown to use RNA editing to
CHROMATIN STRUCTURE AND MODIFICATION • DNA
produce different protein isoforms. The serum protein
TESTING IN FORENSIC SCIENCE • ENZYME MECHANISMS
apolipoprotein B (Apo-B) is expressed in two forms. The
• HYBRIDOMAS,GENETIC ENGINEERING OF • NUCLEIC
Apo-B100 is expressed in hepatocytes, whereas a shorter
ACID SYNTHESIS • RIBOZYMES • TRANSLATION OF RNA
polypeptide, Apo-B48, is expressed in intestinal epithelial
TO PROTEIN
cells. The cell-type-specific expression of Apo-B results
from a posttranscriptional editing of the Apo-B mRNA in
intestinal epithelial cells. Thus, a CAA codon encoding
for the amino acid glutamate is converted to a UAA stop BIBLIOGRAPHY
codon by cytosine deamination. As a result the Apo-B48
protein translated from the edited mRNA in the intestine Lodish, H., Berk, A., Zipursky, S. L., Matsudaria, P., Baltimore, D.,
differs from Apo-B100 by lacking the carboxy-terminus and Darnell, J. (2000). “Molecular Cell Biology,” Freeman and
(Fig. 14). Both proteins bind to lipids. However, only the New York.
liver-specific Apo-B100 contains the carboxy-terminal Latchman, D. S. (1998). “Eukaryotic Transcription Factors,” Academic
Press, San Diego, CA.
domain required for binding to the low-density lipopro-
Gesteland, R. F., Cech, T. R., and Atkins, J. F. (1999). “The RNA World,”
tein receptor, necessary for delivery of cholesterol to body 2nd ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor,
tissues. New York.