2. CONTENTS
Overview of translation
What is proofreading
Proofreading at protein level
Types of proofreading
Previously asked questions
References
3. TRANSLATION
The process of synthesizing an amino acid sequence from messenger rna which carries
information from the genetic material containing genes.
4.
5. Proofreading
Proofreading in translation can be defined as the mechanism which works
simultananeously along with the synthesis of proteins, which helps in the
correction of any incorrect amino acid which charges the trna.
7. CHEMICAL PROOFREADING
It takes place in the pre translational events
Activation of amino acid
Charging of trna
8. This type of editing can also be called as double sieve model , proposed by
Fersht and Kaethner
9. CLASS 1 and CLASS 2 (AARS)
Two classes of AARS (amino acyl trna synthetase) are present which
attaches the amino acids to the trna at different sites. Class 1 attaches the
amino acid at the 2’ end of the trna , whereas the Class 2 AARS attaches
the amino acid at the 3’ end of the trna of the base adenine , as CCA is the
sequence present in the acceptor arm
Class 1 recognises amino acids like – Arg, Cys, Glu, Glutamic acid, leu, iso-
leu, try, where as Class 2 recognises amino acids like – Gly, Pro, Ala, Lys,
Phe etc.
10. KINETIC PROOFREADING
Codon anticodon basepairing
16 rRNA forms H bonds with minor groove of codon : anticodon duplex
only when correctly paired.
Correct base pairing allows EF-TU bound to aa- tRNA to interact with
factor binding center inducing GTP hydrolysis and EF-TU release.
In case of incorrect base pairing FBC ( factor binding site ) will not be
contacted, and will allow more time for EF-TU GTP release
11. Mechanisms that ensure the correct
pairing between tRNA and mRNA
To release EF-TU , its GTP must be hydrolysed . Mismatches in the codon-
anticodon pairing alter the position of EF-TU preventing its interaction
with the factor- binding center and reducing its GTPase activity.
After release of EF-TU, the tRNA must rotate the aa towards the P-site in a
process called accommodation. Incorrectly paired tRNA will often
dissociate in this process.
The error rate of translation is approximately one incorrect amino acids
inserted per 2000 residues
12. Quality control mechanisms
One mechanism of quality control over translation is a type of
proofreading that takes place at the A site.
In the elongation process the charged trna comes to the A site bound with
molecule of EF-TU GTP.
The anticodon of the charged trna has to fit tightly into the active sites to
promote the formation of peptide bonds.
When the codon and anticodon does not match however hydrolysis of GTP
is reduced which allows enough time for the incorrect charged trna to
diffuse away and replaced with the correct ones. This type of proofreading
at A site is called as KINETIC PROOFREADING.
13. SECOND QUALITY CONTROL
A second mechanism of quality control takes at the P site. At this point
there is a second check to determine weather the anticodon of the t-RNA
is correct match to codon in m-RNA.
If the match is correct, elongation proceeds normally
If there is mismatch however it means the last amino acid incorporated
into the polypeptide chain is incorrect.
When there is a mismatch at P site, a slight change in configuration of the
ribosome perturbs the fidelity of the t-RNA selection at the A site.
14. CONT..
One possible outcome of the perturbation is that release factor-2 (RF-2)
can gain access to A site and cause premature termination even though no
termination codon is present.
This type of translational termination due to mis-incorporation error is
greatly enhanced by the presence of release factor -3(RF-3)
15. REFERENCES
Freifelder, Molecular Biology, Narosa Publishing house, 2nd edition .
Benjamin Lewin, Genes IX, Jonas and Barlett Publishers.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3009764/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5095583/
