14 - Lecture 14 Post Transcriptional Control of Gene...

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Post Transcriptional Control of Gene Expression Lecture 14 Post-transcriptional control of gene expression 1. mRNA modifications capping, polyadenylation, splicing editing base modifications cytoplasmic polyadenylation 2. mRNA stability, surveillance 3. translational control 4. localization 5. regulation by small RNAs
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RNA Editing (p.340-341) •after transcription, sequence of mRNA is altered •deletions, insertions, base changes •editing enzymes recognize specific RNA sequences/ structures APOBEC Example: Liver cells Intestinal cells Base Changes Cytosine deamination: Adenosine deamination: Inosine Adenine Cytosine Uracil
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Control of translation by cytoplasmic polyadenylation of mRNAs •short Poly(A)tail •CPE containing - recruitment of Maskin Cytoplasmic PolyA
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Cytoplasmic polyadenylation promotes translation of some mRNAs •signal activates kinase •phosphorylation of CPEB •release of Maskin •recruitment of CPSF & PAP = polyadenylation of mRNA •PABPI binding & stabilization of initiation factors mRNA Stability
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mRNA stability [mRNA] depends on rate of synthesis and destruction typical mRNA half-life: Prok = minutes Euk = hours AU-rich instability elements •typically 3’ UTR •recognized by specific proteins •typically stimulate mRNA deadenylation (removes the 3’ tail) Rate at which eukaryotic mRNAs are degraded offers another point of control Eukaryotic mRNA degradation pathways Rate at which eukaryotic mRNAs are degraded offers another point of control
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Example Iron-dependent regulation of mRNA translation and degradation: Dual control by IRE-BP precisely regulates the level of free iron within cells. Sequence-specific RNA- Binding Proteins Control Specific mRNA Translation The same protein can bind different mRNAs and direct different outcomes Low iron: needs to increase free iron •transferrin receptor expression ON •ferritin expression OFF High iron: needs to prevent accumulation of toxic levels of free iron •Transferrin receptor expression OFF •Ferritin expression ON
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Iron Response Element Binding Protein (IRE-BP) •cannot bind to mRNA (IRE) when bound to iron •location of IRE in mRNA determines regulation Fe Inactive IRE-BP Fe IRE-BP regulation of ferritin mRNA
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Fe IRE-BP regulation of TfR mRNA mRNA Surveillance
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