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            The
central dogma of modern biochemistry is based on the coded information
contained within deoxyribonucleic acid (DNA). 
Double-stranded DNA is converted to single-stranded RNA.  RNA is then converted to a linear strand of
amino acids, which subsequently fold into three-dimensional proteins.  These proteins act as structural components
of cells within the body or as functional biochemical machines.  The building of cellular proteins from the
encoded instructions within DNA occurs in two steps:  transcription and translation.  During transcription, the four nucleotides of
DNA (adenine, cytosine, guanine, and thymine) are rewritten in the form of the
portable messenger ribonucleic acid (mRNA), which is composed of adenine,
cytosine, guanine, and uracil.  The
translation process decrypts this transcribed mRNA code into a linear string of
amino acids.  This procedure is
accomplished by matching transfer RNAs (tRNAs) and their associated amino acid
to the sequence of mRNA nucleotides. 
After the protein has completed translation, it undergoes many
structural changes to fold into its native conformation.  The protein is now ready to play its
functional role in the life of the organism.

To thoroughly
analyze the translation process, we would first begin by examining the
interrelationship between nucleic acid sequences and polypeptide sequences, the
genetic code.  Next, we consider the structures
and properties of tRNAs, the amino acid carriers that mediate the translation
process.  Following this, we consider the
structure and functions of ribosomes, the intricate molecular mechanisms that
catalyze peptide bond formation between the mRNA-specified amino acids.  Finally, we investigate how cells degrade
proteins, a process that must balance protein synthesis.

To decipher the
genetic code, researchers needed to figure out how sequences of nucleotides in
a DNA or RNA molecule could encode the sequence of amino acids in a
polypeptide.  Cells interpret mRNAs by
reading their nucleotides in groups of three, called codons.   Of 64 codons,
there are 61 that are each read to specify a certain amino acid.  The use of repeating tetranucleotides
indicated the reading direction of the code in that mRNAs are read in the 5′ to
3′ direction.   There are three codons that
do not specify amino acids.  These
codons, UAG, UAA, and UGA are chain termination signals known as stop
codons.  The codons AUG, and less
frequently GUG, form part of the chain initiation sequence known as start
codons.  These codons however, also
specify the amino acid residues Met and Val. 

The triplet
character of the genetic code was established through the use of chemical
mutagens, substances that chemically induce mutations.  There are two major classes of mutations:
Point mutations, and insertion/deletion mutations.  Point mutations are changes within a gene in
which one base pair replaces another. 
These mutations are caused by either base analogs that mispair during
DNA replication or by substances that react with bases to form products that
mispair.  During insertion/deletion
mutations, one or more nucleotide pairs are inserted or deleted from DNA.  The insertion or deletion of a nucleotide
shifts the frame (grouping) in which succeeding nucleotides are read as codons.  Insertions or deletions of nucleotides are
therefore also known as frameshift mutations. 
These mutations arise from the association of DNA with intercalating
agents that distort the DNA structure. The analysis of a series of frameshift
mutations that suppress one another established that the genetic code is an unpunctuated
triplet code.

The genetic code
could be determined by simply comparing the base sequence of an mRNA with the
amino acid sequence of the polypeptide it specifies.  However, in the 1960s, techniques for
isolating and sequencing mRNAs had not yet been developed.  Therefore, the elucidation of the genetic
code proved to be a difficult task.       In a cell-free protein synthesizing system,
poly (U) directs the synthesis of poly (Phe), thereby demonstrating that UUU is
the codon specifying Phe.  This was
established in 1961 by Marshall Nirenberg and Heinrich Matthaei, and served as
a major breakthrough in deciphering the genetic code.  The genetic code was elucidated through the
use of polynucleotides of known composition but random sequence, by the ability
of defined triplets to promote the ribosomal binding of tRNAs bearing specific amino
acids, and through the use of synthetic mRNAs of known alternating sequences.  The latter investigations have also
demonstrated that the 5′ end of mRNA corresponds to the N terminus of the
polypeptide it specifies and have established the sequences of the Stop codons.

Degenerate codons differ mostly in the identities of their third base. Small
single-stranded DNA phages such as _X174 contain overlapping genes in different
reading frames.  The genetic code used by
mitochondria differs in several codons from the “standard” genetic code.

Therefore, the “standard” genetic code, although very widely utilized, is not
universal.

Transfer RNAs consist
of 54 to 100 nucleotides that can be arranged in the

cloverleaf secondary
structure.  It is possible for up to 10%
of a tRNA’s bases to be modified.  Yeast
tRNAPhe forms a narrow, L-shaped, three-dimensional structure that resembles
that of other tRNAs. Most of the bases are involved in stacking and

base pairing associations including
nine tertiary interactions that appear to be essential for maintaining the
molecule’s native conformation.  Amino
acids are appended to their cognate tRNAs in a two-stage reaction catalyzed by
the corresponding aminoacyl–tRNA synthetase (aaRS).  There are two classes of

aaRSs, each containing 10 members.

Class I aaRSs have two conserved sequence motifs that occur in the Rossmann
fold common to the catalytic domain of these enzymes. Class II aaRSs have three
conserved sequence motifs that occur in the

7-stranded antiparallel  sheet–containing fold that forms the core of
their catalytic domains.  In binding only
their cognate tRNAs, aaRSs recognize only an idiosyncratic but limited number of
bases (identity elements) that are, most often, located at

the anticodon and in the acceptor
stem. The great accuracy of tRNA charging arises from the proofreading of the
bound amino acid by certain aminoacyl–tRNA synthetases via a double-sieve
mechanism and at the expense of ATP hydrolysis.

Many organisms and organelles lack
a GlnRS and instead synthesize Gln–tRNAGln by the GluRS-catalyzed charging of tRNAGln
with glutamate followed by its transamidation using glutamine as the amido
group source in a reaction mediated

by Glu–tRNAGln amidotransferase
(Glu-AdT).  Ribosomes select tRNAs solely
on the basis of their anticodons. A single tRNA, through wobble pairing, reads
sets of degenerate codons.  The UGA codon,
which is normally the opal Stop codon may, depending on its context in mRNA,
specify a selenoCys (Sec) residue, which is carried by a specific tRNA (tRNASec),
thereby forming a selenoprotein. Nonsense mutations may be suppressed by tRNAs
whose anticodons have mutated to recognize a Stop codon.