Central dogma of Molecular Biology

Francis Crick in 1958 discovered the process of protein synthesis. Crick

called this discovery the Central Dogma of Biology.

The central dogma of molecular biology deals with the detailed residue-by-
residue transfer of sequential information. It states that such information
cannot be transferred back from protein to either protein or nucleic acid.

The central dogma of protein The flow of genetic information in cells from
DNA to mRNA to protein is described by the central dogma. The dogma is a
framework for understanding the transfer of sequence information between
information-carrying biopolymers, DNA and RNA (both nucleic acids),
and protein.

Central Dogma = DNA → RNA → Protein

RNA is a small molecule that can squeeze through pores in the nuclear
membrane. It carries the information from DNA in the nucleus to a ribosome in
the cytoplasm and then helps assemble the protein.
The two processes involved in the central dogma are :

1. Transcription
2. Translation

Transcription
Is the first part of the central dogma of molecular biology: DNA → RNA. It is the
transfer of genetic instructions in DNA to mRNA. The process
of Transcription takes place in the cytoplasm in prokaryotes and in nucleus in
eukaryotes. It uses DNA as a template to make an RNA (mRNA) molecule. During
transcription, a strand of mRNA is made that is complementary to a strand of
DNA.

Transcription takes place in three steps, called initiation, elongation, and

termination
Step 1: Initiation
Initiation is the beginning of transcription. It occurs
when the enzyme RNA polymerase binds to a region
of a gene called the promoter. This signals the DNA
to unwind so the enzyme can ‘‘read’’ the bases in one
of the DNA strands. The enzyme is now ready to
make a strand of mRNA with a complementary
sequence of bases.
Step 2: Elongation
Elongation is the addition of nucleotides to the
mRNA strand. RNA polymerase reads the unwound
DNA strand and builds the mRNA molecule, using
complementary base pairs. During this process, an
adenine (A) in the DNA binds to an uracil (U) in the
RNA.
Step 3: Termination
Termination is the ending of transcription, and occurs
when RNA polymerase crosses a stop (termination)
sequence in the gene. The mRNA strand is complete,
and it detaches from DNA.
In eukaryotes, the new mRNA is not yet ready for translation. At this stage,
it is called pre-mRNA, and it must go through more processing before it
leaves the nucleus as mature mRNA. The processing may include the
addition of a 5' cap, splicing, editing, and 3' polyadenylation (poly-A) tail.
These processes modify the mRNA in various ways. Such modifications allow
a single gene to be used to make more than one protein. 5' cap protects
mRNA in the cytoplasm and helps in the attachment of mRNA with
the ribosome for translation.
Splicing removes introns from the protein-coding sequence of
mRNA. Introns are regions that do not code for the protein. The remaining
mRNA consists only of regions called exons that do code for the protein.
Editing changes some of the nucleotides in mRNA. For example, a
human protein called APOB, which helps transport lipids in the blood , has
two different forms because of editing. One form is smaller than the other
because editing adds an earlier stop signal in mRNA.
Polyadenylation adds a “tail” to the mRNA. The tail consists of a string of
As (adenine bases). It signals the end of mRNA. It is also involved in
exporting mRNA from the nucleus, and it protects mRNA from enzymes that
might break it down.
2. Translation
 It is the second part of the central dogma of molecular biology:
 RNA --> Protein.
It is the process in which the genetic code in mRNA is read to make a protein.
After mRNA leaves the nucleus, it moves to a ribosome , which consists of
rRNA and proteins. Translation happens on the ribosomes floating in
the cytosol , or on the ribosomes attached to the rough endoplasmic
reticulum.
The ribosome reads the sequence of codons in mRNA, and molecules of
tRNA bring amino acids to the ribosome in the correct sequence. Each
tRNA molecule has an anticodon for the amino acid it carries.
An anticodon is complementary to the codon for an amino acid . For
example, the amino acid lysine has the codon AAG, so the anticodon is UUC.
Therefore, lysine would be carried by a tRNA molecule with the anticodon
UUC. Wherever the codon AAG appears in mRNA, a UUC anticodon of tRNA
temporarily binds. While bound to mRNA, tRNA gives up its amino acid.
With the help of rRNA, bonds form between the amino acids as they are
brought one by one to the ribosome, creating a polypeptide chain. The chain of
amino acids keeps growing until a stop codon is reached.
1. Initiation: The small subunit binds to a site upstream (on the 5' side) of the start
of the mRNA. It proceeds to scan the mRNA in the 5'-->3' direction until it
encounters the START codon (AUG). The large subunit attaches and the initiator
tRNA, which carries methionine (Met), binds to the P site on the ribosome.
2. Elongation: The ribosome shifts one codon at a time, catalyzing each process
that occurs in the three sites. With each step, a charged tRNA enters the complex,
the polypeptide becomes one amino acid longer, and an uncharged tRNA departs.
The energy for each bond between amino acids is derived from GTP,
a molecule similar to ATP. Briefly, the ribosomes interact with other RNA
molecules to make chains of amino acids called polypeptide chains, due to the
peptide bond that forms between individual amino acids. Inside the ribosome,
three sites participate in the translation process, the A, P, and E sites. Amazingly,
the E. coli translation apparatus takes only 0.05 seconds to add each amino acid,
meaning that a 200-amino acid polypeptide could be translated in just 10 seconds.
3. Termination: Termination of translation occurs when a stop codon
(UAA, UAG, or UGA) is encountered. When the ribosome encounters the
stop codon , the growing polypeptide is released with the help of various releasing
factors and the ribosome subunits dissociate and leave the mRNA. After many
ribosomes have completed translation , the mRNA is degraded so the nucleotides
can be reused in another transcription reaction.