10.RNAprocessing1

10.RNAprocessing1 - mRNA Processing: Overview Prokaryotes:...

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mRNA Processing: Overview Prokaryotes: mRNAs used as is Eukaryotes: movement of hnRNA (heterogeneous nuclear RNA) into cytoplasm prior to translation Capped at 5’-end Poly-A tail added at 3’-end Introns are removed by splicing
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The life cycle of an mRNA is regulated by  dynamic association with mRNA-binding  proteins. mRNAs navigate the journey from  transcription to translation and degradation as  protein-bound mRNP complexes. In the  nucleus, transcripts are capped, spliced,  cleaved, and polyadenylated by RNA-binding  proteins that interact with the nascent  transcript co- and post-transcriptionally.  Quality control measures ensure that only  properly processed transcripts are exported.  An mRNP is then subject to multiple fates in  the cytoplasm, including subcellular  localization, translation, and degradation, as  predicated by its changing cohort of  associated RNA-binding proteins. Cell Research  (2007)  17: 581 : 590
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hnRNA (aka pre-mRNA): heterogeneous nuclear RNA Newly synthesized RNA right off RNA polymerase II Introns intact mRNA 5’-Cap, 3’-poly-A tail, introns removed
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5’-5’ triphosphate bridge - occurs in cell nucleus - added when hnRNA is 30 nts long - happens while RNA polymerase is still transcribing pre-mRNA - cap helps to define translation start site Cap structure at the 5’ end of eukaryotic mRNAs Fig. 31-43
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Garrett and Grisham Fig. 31.47 Synthesis of the 5’-cap Step 2: Transfer a GMP unit from GTP to a lysine residue in the active site of the guanylyl transferase Step 1: An RNA triphosphatase hydrolyzes the 5’ triphosphate to the diphosphate on the mRNA Step 3: Attack of the β -phosphate on the mRNA on the GMP-Enz bond with the transfer of the GMP moiety to the mRNA EMBO J. 3 (1983) 2195-2201
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Methylations of 5’-Cap Step 4: Sequential methylations using specific methyl transferases SAM Mature 5’ Cap - Guanine-7-methyltransferase: methylation of the capping G base at 7 position - Uses S-adenosylmethionine (SAM) as methyl donor - 2’- O -methyltransferase: methylation of 2’-OH positions on riboses on 1st and 2nd RNA base of mRNA
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Cap I has the 2’-OH on the first residue methylated predominant form Cap II has the 2’-OH’s on the first and second residues methylated Cap structure at the 5’ end of eukaryotic mRNAs Fig. 31-43
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QuickTime and a TIFF (LZW) decompressor are needed to see this picture. www.genomeknowledge.org/figures/Cap1.jpg
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10.RNAprocessing1 - mRNA Processing: Overview Prokaryotes:...

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