Page 94 - Academic Press Encyclopedia of Physical Science and Technology 3rd Molecular Biology

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

Translation of RNA to Protein 35

translated. As with prokaryotic mRNA the coding region only at UGA codons in a particular context of neighboring

is flanked by 5 and 3 nontranslated sequences. nucleotides. The insertion of selenocysteine residues into
the polypeptide also requires a specific elongation factor
T which differs from the factor used for the incorporation
D. The Genetic Code
of other aminoacyl-tRNAs.
The genetic code is triplet, comma-less, and nonoverlap- Mitochondria and chloroplasts, as well as certain organ-
ping. As a consequence, a nucleotide sequence has three isms such as mycoplasma and ciliated protozoa, use a few
possible reading frames (Fig. 4). Because mRNA is nor- nonstandard genetic codons. For example, methionine is
mally translated into a unique polypeptide, an essential usually coded for by AUG (or occasionally by GUG) but
step in the translation process is the selection of the ap- in human mitochondria this codon is replaced by AUA.
propriate reading frame. This is achieved by starting trans- Variations in the genetic code are thought to have arisen
lation at the initiation codon, usually AUG or less fre- as a result of the loss of some tRNA genes and mutational
quently GUG, which ensures that the following codons pressure on DNA, giving rise to a predominance of either
are read in phase within the required reading frame. Of AT- or GC-rich codons.
the 64 theoretically possible triplets in the genetic code,
61 sense codons correspond to the 20 genetically encoded
amino acids found in all, or nearly all, proteins. When III. TRANSFER RNA ∗∗
GUG is used as the initiation codon, it codes for me-
thionine by interacting with the anticodon of the initiator By relating individual codons of mRNA to the cognate
Met-tRNA Met , whereas elsewhere it codes for valine. All amino acids, tRNA functions as a key bilingual interme-
other codons specify only one amino acid but many amino diate in the translation of the genetic code. All transfer
acids are specified by two or more (up to six) codons; the RNAs are single-stranded molecules about 80 nucleotides

code is unambiguous, but degenerate. The remaining three long with a common 3 -terminal CCA sequence. Most of
codons, termed nonsense codons, usually signify termina- the bases are standard but some (e.g., pseudoU, dihydroU,
tion of synthesis and release of the finished polypeptide and T) are derived by modification after transcription of
chain. the transfer RNA genes.
The secondary structure of tRNA is usually presented
in two dimensions as a cloverleaf to highlight the regions
1. Deviations from the Standard Genetic Code of base-pairing (Fig. 5a). X-ray crystallography reveals
One of the nonsense codons, UGA, has an additional that additional hydrogen bonds give rise to an L-shaped
function in the synthesis of selenoproteins. The process tertiary structure (Fig. 5b). The CCA sequence carrying
involves the initial synthesis of selenocysteyl-tRNA from the amino acid is located distal to the anticodon.
a novel seryl-tRNA and selenium. This tRNA contains an The decoding process involves antiparallel base pairing
anticodon that is able to decode UGA and insert seleno- between the three bases of mRNA codons and the comple-
cysteine residues into the growing polypeptide chain, but mentary anticodons of transfer RNA (tRNA) during pep-
tide bond formation (Fig. 6). The first and middle bases

∗ Transfer RNA nomenclature: The amino acid linked to a charged
tRNA is indicated by a prefix and the specificity of the transfer RNA
(tRNA) in the aminoacylation reaction is shown as a superscript on the
right; for example, Phe-tRNA Phe indicates phenylalanine-specific tRNA
charged with phenylalanine. The anticodon may be indicated as a right
subscript or, alternatively, in the superscript after the amino acid; for
example, tRNA UGC or tRNA Ala/UGC . The right-hand subscript position
is sometimes used to indicate the organism from which the tRNA is
derived (e.g., tRNA Val ). The initiator tRNA, which is specific for me-
yeast
thionine, is termed tRNA Met or tRNA Met . In the cytosol of eukaryotes the
f
i
charged initiator tRNA is termed Met-tRNA Met of Met-tRNA Met . Often
f
i
the superscript Met is omitted. In prokaryotes and in the mitochondria
of eukaryotes, the methionine residue of the charged initiator tRNA is
10
formylated by a transformylase using N -formyltetrahydrofolate as the
FIGURE 4 Translation of a polynucleotide sequence into three al- donor, giving N-formylmet-tRNA f . Commonly, this charged tRNA is
ternative polypeptides using different reading frames. [From Cox, termed fMet-tRNA f . The methionine-specific elongator RNA, which in-
R. A., and Arnstein, H. R. V. (1995). In “Encyclopedia of Molecular serts methionine into internal positions of the growing peptide chain,
Biology and Molecular Medicine” (R. A. Meyers, ed.), Volume 6, is termed tRNA Met (or tRNA m ) when uncharged, and Met-tRNA Met
m
m
pp. 108–125. VCH Publishers, New York. With permission.] (or Met-tRNA m ) when charged.