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Control of GENE EXPRESSION

at TRANSLATIONAL LEVEL
INTRODUCTION
Gene expression:-Process by which Information from a gene is used in the
synthesis of a functional gene product.
Or
Gene expression refers to the molecular mechanism by which a gene shows its
potential in the phenotype of an organism.

●Gene expression occur in 2 steps :-


●Transcription
●Translation
●Gene expression begins in nucleus with the process of
transcription , in which the information of the DNA is copied
into RNA i.e mRNA.
●mRNA job is to carry the informatipn outside the nucleus
and use it to perform 2nd step of gene expression known as
Translation.
● In translation the meassage stored on the mRNA is decoded
in a ribosome to produce a specific amino acid chain or
polypeptide.
● Structures important for translation :-

mRNA
tRNA
Ribosome

Ribosome read the message on mRNA .


tRNA transfers individual amino acid to the ribosome.
According to the sequence of base pair on the mRNA these amino
acids are then joined together by bonds to form a protein

●Process of Translation occur in 3 basic steps :-

Initiation:- Ribosome assembles around the target mRNA.


Elongation:- tRNA transfers amino acid to the ribosome which are
joined together to form a polypeptide chain .
Termination:- Ribosome release the polypeptide when it reach the
stop signal on the mRNA .

Stop codon UAG


UAA
UGA
Regulation of Translation
Most of th3 regulation occur in initiation step.
• In prokaryotes
(1) Shine Dalgarno sequence polymorphism :-

nCR= non coding region


SDS= shine dalgarno sequence (4-9 purines)
CR= coding region
● Shine dalgarno sequence helps the pre initiation complex to recognise
AUG codon

● If polymorphism occur in Shine dalgarno sequence ,it leads to


confirmational changes due to which it cannot recognise AUG

● Firstly small subunit of ribosome attach to SDS →then SDS project out
AUG → So that small subunit easily identify AUG and bind to it .
But if changes occur in SDS ribosome cannot identify
AUG → Translation cannot occur .
(2)Initiation factor:- These are various types of proteins that bind with
small subunit of ribosome → initiation start.
• Initiation factor help tRNA (formulated methionine ) to bind with
initiation codon
tRNA + initiation codon
•IF1 + 30S ribosome → change confirmation of ribosome → bind easily
to IF2 and IF3
• IF2 arrange tRNA (F.met.) to correct position.
• IF3 helps in proof reading.
If these changes occur ,initiation can be done properly ,if cannot
initiation stop.
(3) Diminished tRNA pool:- reduce translation efficiency .

•Elongation process is irreversible ,but if tRNA is less in cytoplasm →


translation efficiency is reduce

(4)Bases near to stop codon:- UAA,UAG,UGA are stop codons

Eg:- Termination efficiency for UAAU =80%


Termination efficiency for UGAC=7%
Regulation of translation in Eukaryotes
(1)Capping:- mRNA with modified cap(without guanosine residue)→
no translation

(2)mRna processing(splicing) must be absolutely precise :-


•Newly formed mRNA has 2 parts i.e.intron and extron
•Introns exclude out ,exon attaches to each other and form processed
mRNA which comes out from nucleus and start translation in
cytoplasm.
•If intron parts present in processed mRNA ,translation cannot occur.
(3)Introns:-
•Play role in identify and ticketing the molecule that are to be passed
out of nucleus .
•If this done only then processed mRNA comes out of nucleus and
translatipn occur.

(4)Message degradation rates are significant:-


•cessation of specific translation.
•Those mRNA which comes out of nucleus→ some of them can
degrade→ rate of their degradation determine how translation occur
(fast or slow ).
(5)Recruitment factor :-
•Help in formation of ribosome mRNA complex ,if this complex form
only then initiation occur.
Eg :- Rate of protein synthesis in egg is low because these factors are
less in number in egg or cannot express properly.

(6)Ferrous ion:-
•Ferrous ion bind with storage protein and form ferritin.
Ferrous ion + storage protein→ ferritin
•If more is ferrous ion ,more will be ferritin and rate of translation is
also more
•If ferrous ion less,translational repressor form this will block
attachment of mRNA to ribosome and lead to prevention of translation.
(7)Upstream RNA secondary structure complex:-
•If RNA secondary structure is complex towards upstream region ,then
initiation inhibit.

(8)Eukaryotic initiation factors (eIFs):-


(a)eIF4E + 5,7- methylguanylate cap → active translation

(b) eIF2→ help in binding of


Met-tRNA+ P site of ribosome → initiation continue

(c) eIF2- phosphorylatipn→ terminate initiation


Elongation
(9) eEF(eukaryotic elongation factor):-
•eEF2 → It is GTP dependent translocase.
Translocase newly formed polypeptide chain from A to P site.
After translocation A site become free,again tRNA attach to it
If this translocation cannot done,there will be no translation.

(10)Phosphorylation of threonine 56:-


• It inhibit binding of eEF2+ ribosome ,elongation stop
• Occur during stress and anoxia.
Termination
(11)Termination leaky :-
• If termination occur not accuratelt termed as leaky termination.
•If non coding tRNA compete releasing factor (which terminate
translation)→ compete only when starting 2 base of a codon are tge
anticodons of stop codon
Like :- UAA → AUC
|
compete releasing factor and prevent releasing factor to
terminate translation → this will regulate translation.
ROLE OF CHROMATIN IN GENE EXPRESSION

Chromatin:- Chromatin is the complex combination of DNA and proteins


that makes up chromosomes .

Tyes of chromosomes :-
Heterochromatin :- Has condensed chromatin structure and is inactive for
transcription and translation.
•Present at central part of nucleus.

Euchromatin:- Has loose chromatin structure and active for transcription


and tranlation.
•Present at periphery of nucleus.
• Histone protein :- +vely chaarged .
•They acts as spools around which DNA winds to create structural units
called nucleosomes .
•Histone + DNA → Heterochromatin
•Histone remove from DNA → DNA uncoil → become thread like called
Euchromatin

•Histone Deacetyl transferase(HDAC):-


•Remove acetyl group from histone .
•If HDAC remove acetyl group from histobe → histone remain attach to
DNA → form heterochromatin → silence gene expression
REPRESSION OF GENE ACTIVITY BY HISTONES:-
•The binding of histones to form chromatin,represses gene expression
by DNA compaction.
Two classes of protein complexes causes remodeling.

(a)Histone acetyl tranferase(HAT):- it adds acetyl group on histone→ when acetyl group add on histone→
histone leave DNA and attach with acetyl group → DNA open up → form euchromatin → active for gene
expression.
•HATs are recruited to DNA by transactivators and acetylate terminal lysines on histones ,reducing their affinity
for DNA

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