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preface
RNA is synthesized by a DNA dependent RNA polymerase (uses DNA as a
template for the synthesis of RNA). Important terminology used when discussing
transcription is illustrated below.
• RNA polymerase locates genes in DNA by searching for promoter regions.
The promoter is the binding site for RNA polymerase. Binding establishes
where transcription begins, which strand of DNA is used as the template,
and in which direction transcription proceeds. No primer is required.
• RNA polymerase moves along the template strand in the 3′ to 5′ direction
as it synthesizes the RNA product in the 5′ to 3′ direction using NTPs
(ATP, GTP, CTP, UTP) as substrates. RNA polymerase does not proofread
its work. The RNA product is complementary and antiparallel to the
template strand.
• The coding (antitemplate) strand is not used during transcription. It is
identical in sequence to the RNA molecule, except that RNA contains
uracil instead of the thymine found in DNA.
• By convention, the base sequence of a gene is given from the coding strand
(5′→3′).
• In the vicinity of a gene, a numbering system is used to identify the
location of important bases. The first base transcribed as RNA is defined
as the +1 base of that gene region.
– To the left (5′, or upstream) of this starting point for transcription,
bases are –1, –2, –3, etc.
– To the right (3′, or downstream) of this point, bases are +2, +3, etc.
• Transcription ends when RNA polymerase reaches a termination signal.
PRODUCTION OF PROKARYOTIC MESSENGER RNA
The structure and expression of a typical prokaryotic gene coding for a protein are
illustrated in Figure I 3 4. The following events occur during the expression of this
gene:
Behavioral Science/SocialSciences
1. With the help of sigma factor, RNA polymerase recognizes and binds to the
promoter region. The bacterial promoter contains two “consensus” sequences,
called the Pribnow box (or TATA box) and the –35 sequence. The promoter
identifies the start site for transcription and orients the enzyme on the tem
plate strand. The RNA polymerase separates the two strands of DNA as it reads
the base sequence of the template strand.
2. Transcription begins at the +1 base pair. Sigma factor is released as soon as
transcription is initiated.
3. The core polymerase continues moving along the template strand in the 3′ to 5′
direction, synthesizing the mRNA in the 5′ to 3′ direction.
4. RNA polymerase eventually reaches a transcription termination signal, at
which point it will stop transcription and release the completed mRNA mol
ecule. There are two kinds of transcription terminators commonly found in
prokaryotic genes:
• Rho independent termination occurs when the newly formed RNA folds
back on itself to form a GC rich hairpin loop closely followed by 6–8 U
residues. These two structural features of the newly synthesized RNA
promote dissociation of the RNA from the DNA template. This is the type
of terminator shown in Figure I 3 4.
• Rho dependent termination requires participation of rho factor. This
protein binds to the newly formed RNA and moves toward the RNA
polymerase that has paused at a termination site. Rho then displaces RNA
polymerase from the 3′ end of the RNA.
5. Transcription and translation can occur simultaneously in bacteria. Because
there is no processing of prokaryotic mRNA (no introns), ribosomes can begin
translating the message even before transcription is complete. Ribosomes bind
to a sequence called the Shine Dalgarno sequence in the 5′ untranslated region
(UTR) of the message. Protein synthesis begins at an AUG codon at the begin
ning of the coding region and continues until the ribosome reaches a stop
codon at the end of the coding region.
6. The ribosome translates the message in the 5′ to 3′ direction, synthesizing the
protein from amino terminus to carboxyl terminus.
here are two genes for the beta chain of hemoglobin. In β thalassemia, there
is a deficiency of β globin protein compared with α globin. A large number of
β globin mutations have been described, including gene deletions, mutations
that slow the transcriptional process, and translational defects involving
nonsense and frameshift mutations. Other mutations involve β globin mRNA
processing (more than 70% of the β globin gene is not encoding information
and eventually must be spliced out), such as splice site mutations at the
consensus sequences. Also, mutations within intron 1 create a new splice site,
resulting in an abnormally long mRNA.
A 9 month old infant of Greek descent was brought to the hospital by
his parents because he became pale, listless, and frequently irritable. The
attending physician noted that the spleen was enlarged and that the infant
was severely anemic. His face had unusual features with large cheekbones
due to deformities in the skull.
β thalassemias are found primarily in Mediterranean areas. It is believed
that, similar to sickle cell anemia and glucose 6 phosphate dehydrogenase
deficiency, the abnormality of red blood cells in β thalassemia may protect
against malaria. Splenomegaly is due to the role of the spleen in clearing
damaged red cells from the bloodstream. The excessive activity of the bone
marrow produces bone deformities of the face and other areas. The long
bones of the arms and legs are abnormally weak and fracture easily. The most
common treatment is blood transfusions every 2–3 weeks, but iron overload is
a serious consequence.
