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Encyclopedia of Physical Science and Technology EN013D-617 July 27, 2001 11:42

240 Protein Synthesis

Nonribosomal peptide synthetases (NRPSs) are large sole contributor of ribosomal function, the results are at
modular proteins that assemble the amino acid units of bestsuggestive.However,thepotentialforRNA-catalyzed
the metabolites. Each module is responsible for a single peptide bond formation is clear. In Darwinian-like exper-
catalyticstep,suchasactivatinganaminoacidtoitsadeny- iments that select functional RNAs from large popula-
late, forming a peptide bond, or modifying a functional tions of partially randomized sequences, researchers have
group. The growing peptide is covalently attached to each identified ribozymes that hydrolyze an aminoacyl ester,
module in turn, and the N- to C-terminal order of modules aminoacylate a tRNA, and form an amide bond between
determines the organization of the final peptide product. two amino acids. For example, such a selected ribozyme
For example, the penicillin precursor ACV is synthesized is able to catalyze formation of an amide bond between an
from modules specific for adenylate formation and attach- AA–tRNA mimic and a peptidyl–tRNA mimic. Interest-
ment of amino adipate, cysteine, and valine, in that order. ingly, this selected peptidyl transferase ribozyme contains
As more genes for NRPSs are identified, it should be pos- some sequence and secondary structure elements of the
sible to rationally construct novel nonribosomal peptides region of E. coli 23S rRNA responsible for peptide bond
by genetic manipulation of modules. formation.

XVI. PROTEIN SYNTHESIS
AND THE RNA WORLD SEE ALSO THE FOLLOWING ARTICLES

HYDROGEN BOND • MACROMOLECULES,STRUCTURE •
In considering questions of the origins of life, many re-
PROTEIN STRUCTURE • RIBOZYMES • TRANSLATION OF
searchers have speculated that RNA was the earliest form
RNA TO PROTEIN
of life, bridging the gap between a prebiotic era and
the modern world of protein catalysts and DNA infor-
mation storage. This suggestion initially came from the
discovery of naturally occurring catalytic RNAs such as BIBLIOGRAPHY
the Tetrahymena ribozyme and the RNA component of
a tRNA processing enzyme known as RNase P. Even in Buckingham, R. H., Grentzmann, G., and Kisselev, L. (1997). “Polypep-
extant systems, many enzyme cofactors have nucleotide tide chain release factors,” Mol. Microbiol. 24, 449–456.
Dever, T. E. (1999). “Translation initiation: Adept at adapting,” Trends
or nucleotide-like components, such as ATP, NADH, and
Biochem. Sci. 24, 398–403.
FAD. Furthermore, RNA both carries genetic information Ibba, M., and S¨oll, D. (1999). “Quality control mechanisms during trans-
(mRNA) and performs catalysis (ribozymes). lation,” Science 286, 1893–1897.
Ifthe“RNAworld”hypothesisiscorrect,whatevidence Martinis, S. A., Plateau, P., Cavarelli, J., and Florentz, C. (1999).
istherethatearlyproteinsynthesismechanismswereRNA “Aminoacyl-tRNA synthetases: A family of expanding functions,”
EMBO J. 18, 4591–4596.
controlled? First, there are three types of RNA that play
Musier-Forsyth, K., and Schimmel, P. (1999). “Atomic determinants for
major roles in translation—mRNA, which contains the aminoacylation of RNA minihelices and relationship to genetic code,”
genetic information; tRNA, the “adaptor” molecule; and Acc. Chem. Res. 32, 368–375.
rRNA, which comprises about 2/3 the mass of the ri- Nissen, P., Kjeldgaard, M., and Nyborg, J. (2000). “Macromolecular
bosome. Mechanistically, some of the catalytic steps of mimicry,” EMBO J. 19, 489–495.
Pennisi, E. (1999). “The race to the ribosome structure,” Science 285,
protein synthesis have been mimicked using only RNA.
2048–2051.
Although several researchers have tried to demonstrate Yarus, M. (1999). “Boundaries for an RNA world,” Curr. Opin. Chem.
unequivocally that rRNA of modern organisms is the Biol. 3, 260–267.