Translation regulation complete.

1. Presented by
Amna Shahzadi

2. Introduction
Control of gene expression at the level of translation
can occur by:
Differential mRNA Longlivety
Selective Inhibition of mRNA Translation (Stored
oocyte mRNAs)
micro-RNAs
Cytoplasmic Localization
Stored mRNAs in Brain Cells

3. Differential mRNA Longlivety
The longer an mRNA persists, the more protein can be
translated from it.
More time in cytoplasm = More translation
Poly A-tail (post transcriptional processing/on 3’ end)
increases the life of mRNA.

4. Differential mRNA Longlivety
In female rats, caesin (milk protein)mRNA is
normally short lived.
But when the rat is lactating (feeding milk to babies),
prolactin is released.
Prolactin increases the life of caesin mRNA.

5. Selective Inhibition of mRNA
Translation: Stored oocyte mRNAs
The oocyte makes and stores mRNAs that will be used
only after fertilization.
These mRNAs remain dormant.
 They are activated when ovulation/fertilization takes
place (depending on mRNA).

6. Selective Inhibition of mRNA
Translation: Stored oocyte mRNAs
These stored mRNAs encode proteins that:
Are needed during cleavage.
Regulate the timing of early cell division.
Determine the fates of cells. These include the bicoid,
caudal, nanos, etc. in Drosophila.

7. Selective Inhibition of mRNA
Translation: Stored oocyte mRNAs
mRNAs are in cytoplasm, hence they are available for
translation.
 Inhibitors prevent the translation of these mRNAs in
the oocyte
These inhibitors must be removed at the time around
fertilization.

8. Selective Inhibition of mRNA
Translation: Stored oocyte mRNAs
Before fertilization, inhibitors such as Maskin inhibit
translation of mRNA. But upon fertilization, Maskin
(inhibitor) is displaced by an enzyme, translation can
now proceed.

9. micro-RNAs
microRNAs (miRNAs) are RNAs of about 22
nucleotides.
Made from precursor RNA.
They form a RNA-protein complex: RNA induced
silencing complex (RISC) and bind with a target
mRNA (with complementary base pairs) and inhibit
translation.

10. micro-RNAs (Synthesis)
The miRNA gene encodes a pri-miRNA (primary
micro RNA) that has several hairpin regions.
The pri-miRNA is processed into individual pre-
miRNA "hairpins" by a RNAase enzyme.
 These pre-miRNA hairpins are exported from the
nucleus.

11. micro-RNAs (Synthesis)
Once in the cytoplasm, another RNAase,separates the
single stranded miRNA.
›The strand is packaged with proteins into the RNA-
induced silencing complex (RISC).
›RISC binds with target RNA to inhibit translation.

12. micro-RNAs
Model for the formation
and use of microRNAs.

13. micro-RNAs (Action)
The miRNA complex can
inhibit tanslation by:
 Blocking binding of RNA
with ribosomes or initiation
factors.
 Recruiting endonucleases to
Digest poly A tail of target
RNA, this will destroy it.
 Recruiting proteases to
destroy nascent (in process)
protein.

14. Cytoplasmic Localization
A majority of mRNAs (about 70% in Drosophila
embryos) are localized to specific places in the cell .
There are three major mechanisms for the localization
of an mRNA:
Diffusion & Local Anchoring
Localized Protection
Active transport along cytoplasm

15. Cytoplasmic Localization
Diffusion & Local Anchoring:
The nanos (mRNA), produced in
Drosophila oocyte, are free to roam
around the cytoplasm, but they when
they reach the posterior end, they are
anchored and their translation is
initiated.

16. Cytoplasmic Localization
Localized Protection:
The hsp83 mRNA is degraded in all
regions of Drosophila embryo
except the posterior region where it
is offered protection and is
Translated.

17. Cytoplasmic Localization
 Active Transport Along
The Cytoskeleton:
In Drosophila oocyte, bicoids
(mRNAs) are actively (using ATP)
transported to the anterior portion
by the cytoskeleton.

18. Stored mRNAs in Brain Cells
The storage of long-term memory, in brain, requires
new protein synthesis.
 The local translation of mRNAs in the dendrites of
brain neurons, increases the strength of synaptic
connections.

19. Stored mRNAs in Brain Cells
One of the proteins responsible for constructing
specific synapses is brain-derived neurotrophic
factor, or BDNF.
BDNF regulates neural activity and is critical for new
synapse formation.
BDNF induces local translation of previously
mentioned neural messages in the dendrites.

20. Stored mRNAs in Brain Cells
Several mRNAs are transported along the cytoskeleton
to the dendrites of neurons.
These include RNAs coding for:
Receptors for neurotransmitters
Enzymes
Cytoskeleton Components

21. Post-translational Regulation of
Development
Several changes can take place in a protein even after
translation:
Cleavage of inhibitory sections (to activate protein).
Transporting proteins to their required location
(where they have to function).
Assembling with other proteins (Haemoglobin
consists of 4 peptide chains).
Attachment of cofactor (i.e. ions like Ca2+)