30 - RNA Processing; Post-Transcriptional & Pre-Translational Control

30 - RNA Processing; Post-Transcriptional & Pre-Translational Control

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1 Transcription initiation Direct influence of A and R on initiation Chromatin remodeling and histone modifications Methylation Hormones and other “external” signals RNA processing Alternative splicing and trans-splicing polyadenylation Transport through the nuclear pore Posttranscriptional / pretranslational control (events on/with mRNA before ribosomes) Localization of mRNA RNA editing Post-transcriptional silencing by siRNA or miRNA Translational control switch RNA stability (degradation and stabilization) Translational control (mRNA/ribosomes) Phosphorylation of translation initiation factors Upstream AUG codons IRES Protein activity control Posttranslational modification and transport Control of gene expression: overall Alberts, 4 th edition
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2 Nuclear envelope is perforated by pores that can selectively transport macromolecules across the membrane (both direction) Only functional mRNAs are exported Transport through Nuclear Pores 5‟ cap is recognized by transport machinery – it‟s necessary for transport Recall: in nucleus the pre-mRNAs do not exist as free molecules: associated with proteins- hnRNPs Some proteins associated with processed mRNA - nuclear mRNPs (messenger RNPs) are exported together with mRNA into cytoplasm As mRNA-nuclear mRNPs pass through nuclear pore, nuclear mRNPs get replaced with cytoplasmic mRNPs Nuclear proteins shuttle back Cell , Volume 136, Issue 4, 20 February 2009, Pages 777-793 EJC = exon junction complex PABP II PABP II I
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3 Theory: cell has a system that prevents the exit of unspliced mRNA Proof through viral expression- first phases in HIV infection: only a few of viral mRNAs are fully spliced (host machinery used); they are exported to cytoplasm and translated into viral proteins -Among them is Rev mRNA protein is synthesized - Rev protein goes back to the nucleus , binds to the specific sequence in the viral mRNA and helps un-spliced viral mRNAs to go to the cytoplasm through interaction with nuclear export protein -Transported un-spliced viral mRNAs are packed into new viral particles in the cytoplasm Transport through Nuclear Pores is linked to splicing And V mRNA packed into new viral particles
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Control of gene expression: overall Transcription initiation •Direct influence of A and R on initiation •Chromatin remodeling and histone modifications •Methylation •Hormones and other “external” signals RNA processing •Alternative splicing and trans-splicing •polyadenylation Transport through the nuclear pore Posttranscriptional / pretranslational control (events on/with mRNA before ribosomes) •Localization of mRNA •RNA editing •Post-transcriptional silencing by siRNA or miRNA •Translational control switch •RNA stability (degradation and stabilization) Translational control (mRNA/ribosomes) •Phosphorylation of translation initiation factors •Upstream AUG codons •IRES Protein activity control •Posttranslational modification and transport Alberts, 4 th edition
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30 - RNA Processing; Post-Transcriptional & Pre-Translational Control

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