lec 10 - Post-transcriptional mechanisms Key concepts...

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Post-transcriptional mechanisms
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Key concepts Pivotal role of the CTD of the large subunit of RNA polymerase II in RNA processing. Five different snRNPs interact via base pairing with one another and with pre-mRNA to form a structure called the spliceosome. The spliceosome catalyzes two transesterification reactions that join two exons and remove the intervening intron as a lariat structure, which is degraded.
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Base-pairing between pre-mRNA, U1 snRNA, and U2 snRNA is essential for splicing.
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o composed of ~70 proteins, some associated with snRNPs, others not Example: U2AF has 2 subunits, one binds to the pyrimidine-rich region near the 3’ end of introns and to the U2 snRNP. The other subunit binds the AG at the 3’ end of the introns. Thus U2AF promotes interaction of the U2 snRNP with the branch point.
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Release of U1 and U4 makes the spliceosome catalytically active.
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U6 and U2 catalyze the first transesterification reaction. Intermediate contains a 2’-5’ phosphodiester bond.
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This reaction joins the 5’ and 3’ exons by a standard 3’, 5’ phosphodiester bond.
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This is rapidly degraded.
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Interaction of SR (Ser-Arg rich) proteins with exonic splicing enhancers helps define true splice sites.
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