Page 109 - Academic Press Encyclopedia of Physical Science and Technology 3rd Molecular Biology

P1: GTQ Final pages
Encyclopedia of Physical Science and Technology EN017F-788 August 3, 2001 16:27

50 Translation of RNA to Protein

translational error frequency in the presence of the antibi- nucleic acid uses the protein-synthesizing machinery of
otic streptomycin. the host cell and thereby changes normal cell metabolism
To what extent reversible modifications of ribosomal in favor of the synthesis of viral proteins needed for the
constituents are involved in translational control of pro- production of virus progeny.
tein synthesis is uncertain. Although phosphorylation of The polypeptide chains of all proteins are synthesized
ribosomal protein S6 increases with cell proliferation, it by the process described above. This mechanism gives
is not known whether this change is directly related to the rise to primary polypeptide chains, which are often further
accompanying increase in protein synthesis by an effect modified—for example, by cleavage into smaller peptides,
on the translation rate. by structural modification of selected amino acid residues,
by splicing of the polypeptide chain, or by the formation
of covalent bonds between polypeptide chains. Some of
H. Ribosome-Inactivating Proteins
these secondary modifications are related to the correct
Many molds and plants produce toxins, which are pro- folding of polypeptide chains and to the production of
tective reagents, termed ribosome-inactivating proteins active enzymes or peptide hormones from inactive pre-
(RIPs), directed at particular cells and their ribosomes. cursors (e.g., insulin from proinsulin). Also, the transport
These toxins are classified as either type I or type II RIPs of proteins within the cell or the secretion of extracellular
according to the number of polypeptide chains. proteins is often linked to structural changes in polypep-
Type I RIPs comprise a single polypeptide chain; for tide chains either during or after completion of synthesis.
example, α-sarcin, an extracellular cytotoxin produced by
Aspergillus giganteus, consists of a single chain of 150
amino acid residues. SEE ALSO THE FOLLOWING ARTICLES
Type II RIPs comprise two polypeptide chains, A and
B. The A chain has the ability to inactivate ribosomes, and BIOMATERIALS,SYNTHESIS,FABRICATION, AND APPLI-
the B chain is a galactose-specific lectin responsible for the CATIONS • CELL DEATH (APOPTOSIS) • CHROMATIN
entry of the toxin into the target cell. Ricin, which is iso- STRUCTURE AND MODIFICATION • DNA TESTING IN
lated from castor beans, is representative of type II RIPs. FORENSIC SCIENCE • GENE EXPRESSION,REGULATION OF
Ribosomes are inactivated as a result of the RNA • NUCLEIC ACID SYNTHESIS • PROTEIN FOLDING • PRO-
N-glycosidase activity of RIPs. These toxins have TEIN SYNTHESIS • RIBOZYMES
different specificities for particular cells and ribosomes.
However, the target site for all RIPs is an adenylate
residue (position 2660 in the E. coli 23S rRNA sequence) BIBLIOGRAPHY
located within a highly conserved sequence of 12

nucleotides (5 AGUACGAGAGGA 2665 3 ). Cleavage Al-Karadaghi, S., Kristensen, O., and Liljas, A. (2000). “A decade of
2654
of the GpA 2660 internucleotide bond or depurination of progress in understanding the structural basis of protein synthesis,”
A 2660 is sufficient to inactivate the ribosome. The target Progr. Biophys. Mol. Biol. 73, 167–193.
Arnstein,H.R.V.,andCox,R.A.(1992).“ProteinBiosynthesis,”Oxford
residue is located in the loop region of a stem–loop
University Press, London.
element of secondary structure which is termed the Ban, N., Nissen, P., Hansen, J., Moore, P. B., and Steitz, T. A. (2000).
α-sarcin stem–loop. Thus, the target adenylate is either “The complete atomic structure of the large ribosomal subunit at 2.4
directly or indirectly essential for ribosome function. The ˚ A resolution,” Science 289, 905–920.
α-sarcin stem–loop is known to be important for binding Carter, A. P., Clemons, W. M., Brodersen, D. E., Morgan-Warren, R. J.,
Wimberly, B. T., and Ramakrishnan, V. (2000). “Functional insights
elongation factors EF-Tu and EF-G to the ribosome. RIPs
from the structure of the 30S ribosomal subunit and its interactions
have attracted interest as active components of reagents with antibiotics,” Nature 407, 340–349.
directed at particular targets such as cancer cells. Garrett, R. A. et al., eds. (2000). “The Ribosome: Structure, Function,
Antibiotics and Cellular Interactions,” American Society for Micro-
biology, Washington, D.C.
Green, R., and Noller, H. F. (1997). “Ribosomes and translation,” Annu.
VI. CONCLUDING REMARKS
Rev. Biochem. 66, 674–716.
Grunberg-Manago, M. (1999). Messenger RNA stability and its role
The control of protein synthesis, either by regulation of in control of gene expression in bacteria and phages,” Annu. Rev.
the amount of mRNA available for translation or by the Genetics 33, 193–227.
efficiency with which it is translated, is important in cell Hardesty, B., and Kramer, G. (2001) “Folding of a nascent peptide on
the ribosome,” Progr. Nucleic Acid Res. Molec. Biol. 66, 41–66.
growth and development as a factor determining the level
Herr, A. J., Atkins, J. F., and Gesteland, R. F. (2000). “Coupling of open
of cellular and extracellular proteins. Subversion of this reading frames by translational bypassing,” Annu. Rev. Biochem. 69,
control occurs in cells infected by viruses when the viral 343–372.