Gallouzi 454 Sept 19 2011

Gallouzi 454 Sept 19 2011 - How does mRNA half-life affects...

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How does mRNA half-life affects gene expression?
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Eukaryotic mRNA decay pathways Importance of mRNA turnover 1- regulates protein levels (e.g. c-fos levels leads to cancer) 2- eliminates aberrant mRNAs (e.g. β -Thalassemia) 3- essential host-defense mechanism during viral infection Nomenclature mRNA turnover mRNA surveillance RNA interference 5 ` - 3 ` 3 ` - 5 ` NMD NSD siRNA miRNA Translation inhibition Translation required
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Mechanisms of mRNA decay A) Normal mRNAs are degraded by different pathways. B)Nonsense-Mediated decay B)Nonstop decay Transcripts lacking a termination codon are degraded by the exosome in a deadenylase-independent manner. A premature stop codon triggers rapid decapping and 5' to 3' exonucleolytic digestion. 50 nt
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Degradation mRNA Translation Translation efFciency depends on mRNA levels - mRNA degradation is tightly regulated - Dependent on cis -acting sequences and trans -acting factors - Transcription - Processing - Export
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mRNA degradation - Most mRNA species have a half-life of about 4h . - Some mRNA species have very long half lives if they can be protected from ribonucleases (RNases) by proteins or RNA secondary structure. - Some mRNA species have very short half lives due to the presence of destabilizing elements in their 3 ` UTR. These elements render mRNAs accessible to ribonucleases under certain conditions.
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- Alternatively, mRNAs can be cleaved by endonriboucleases and those fragments could be degraded from both ends. Normal mRNAs are degraded by
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Gallouzi 454 Sept 19 2011 - How does mRNA half-life affects...

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