10_11 - Processing of eukaryotic pre-mRNA For primary...

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Processing of eukaryotic pre-mRNA Human dystrophin gene has 79 exons, spans over 2,300-Kb and requires over 16 hours to be transcribed! For primary transcripts containing multiple exons and introns, splicing occurs before transcription of the gene is complete--co- transcriptional splicing.
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Sometimes methylated Sometimes methylated The cap is added after the nascent RNA molecules produced by RNA polymerase II reach a length of 25- 30 nucleotides. •Guanylyltransferase is recruited and activated through binding to the Ser5- phosphorylated Pol II CTD. • The methyl groups are derived from S- adenosylmethionine. • Capping helps stabilize mRNA and enhances translation, splicing and export into the cytoplasm. Capping of the 5’ end of nascent RNA transcripts with m 7 G Existing in a single complex
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Polyadenylation of mRNA at the 3’ end CPSF: cleavage and polyadenylation specificity factor. CStF: cleavage stimulatory factor. CFI & CFII: PAP: poly(A) polymerase. PABPII: poly(A)-binding protein II. Poly(A) tail stabilizes mRNA and enhances translation and export into the cytoplasm. RNA is cleaved 10~35-nt 3’ to A 2 UA 3 . The binding of PAP prior to cleavage ensures that the free 3’ end generated is rapidly polyadenylated. PAP adds the first 12A residues to 3’-OH slowly. Binding of PABPII to the initial short poly(A) tail greatly accelerates polyadenylation by PAP. The polyadenylation complex is associated with the CTD of Pol II following initiation.
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Consensus sequences around 5’ and 3’ splice sites in vertebrate pre-mRNAs The central region of the intron, which may range from 40 bases to 500 kilobases in length, generally is unnecessary for splicing to occur.
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Thalassemia: a group of inherited anemias characterized by defective synthesis of hemoglobin (O 2 -transporter with α 2 β 2 subunits) is caused by
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10_11 - Processing of eukaryotic pre-mRNA For primary...

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