Presentation 8-9-9-11

Presentation 8-9-9-11 - Presentation 8 "Chapter 21 ! RNA...

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1 RNA Splicing and Processing Topics Alternative splicing, Drosophila Sex determination pathway Mis-splicing and cancer Trans -Splicing reactions use small RNAs 3’ end formation 3’ mRNA end processing is critical for transcriptional termination T-RNA splicing “Introns early” “Introns late” models Presentation 8 Chapter 21 Optional reading Pg 47
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2 Fas receptor (also known as tumor necrosis factor receptor [TNFR]) Multiple isoforms of the Fas receptor protein are produced by alternative splicing. Two normally occurring isoforms in humans are produced by an exon-skipping mechanism. An mRNA including exon 6 encodes the membrane-bound form of the Fas receptor, which promotes apoptosis (programmed cell death). [Increased expression of Fas receptor in skin cells chronically exposed to the sun, and absence of expression in skin cancer cells, suggests that this mechanism may be important in elimination of pre- cancerous cells in humans.] If exon 6 is skipped, the resulting mRNA encodes a soluble Fas protein that does not promote apoptosis. The inclusion or skipping of the exon depends on two antagonistic proteins, TIA-1 and polypyrimidine tract-binding protein (PTB) . The 5' donor site in the intron downstream from exon 6 in the pre- mRNA has a weak agreement with the consensus sequence, and is not bound usually by the U1 snRNP. If U1 does not bind, the exon is skipped.
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3 Fas receptor Binding of TIA-1 protein to an intronic splicing enhancer site stabilizes binding of the U1 snRNP. The resulting 5' donor site complex assists in binding of the splicing factor U2AF to the 3' splice site upstream of the exon. Exon 6 contains a pyrimidine-rich e xonic s plicing s ilencer, ure6 , where PTB can bind. If PTB binds, it inhibits the effect of the 5' donor complex on the binding of U2AF to the acceptor site, resulting in exon skipping.
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4 In addition… To GU…AG Splicing Depends on: ESE Exonic Splicing Enhancers SR Splicing Regulatory proteins DNA sequence motif consisting of 6 bases within an exon that directs, or enhances, accurate splicing of pre-mRNA into messenger RNA (mRNA).
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5 Pathway of Sex Determination in D. melanogaster Uses alternative splicing patterns to specify male and female sexes.
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This note was uploaded on 09/25/2011 for the course GEN 409 taught by Professor Linda during the Spring '09 term at Iowa State.

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Presentation 8-9-9-11 - Presentation 8 "Chapter 21 ! RNA...

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