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Lecture-6-RNA-modifification

Lecture-6-RNA-modifification - NUCLEIC ACID BIOCHEMISTRY...

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NUCLEIC’ACID’BIOCHEMISTRY’ BCHS’4306’ Lecture’6:’ RNA-splicing/RNA-modiGication-Editing’
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The’Central’Dogma’ Germline’ (Gametes)’ Somatic’Cells’ Meiosis’ Mitosis’ Express’traits’ Transmit traits
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A’View’of’the’Gene’Structure’in’Eukaryotes’ Transcription’always’occurs’in’the’5 ` ’to’3 ` ’direction’just’like’replication’ Genes’are’split’
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Questions to ponder today Why is it advantageous to have split genes that then have to be spliced We can increase genome complexity without increasing the number of genes Allows us to increase genome complexity without increasing gene number 30,000 genes/human genome – many isoforms…100,000 coding RNA We can exert more control over gene expression
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Genes Transcription Genes on the same chromosome can be transcribed in different directions. Each gene is always transcribed only in one direction.
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Chromosome 1 Allele’C’ Allele’-’A’ Allele’-’B’ 5±’ 3±’ 3±’ 5±’ Allele’C’ Allele’-’A’ Gene’b’ 5±’ 3±’ 3±’ 5±’ Paternal’Homolog’ Maternal’Homolog’ Gene’A’ Allele’-’b’ Gene’B’ Gene’C’ Coding strand of allele B =’5±-ATGGCTATGAGTTCAGTCC-3±’ Coding strand of allele b ’=’5±-ATGGC a ATGAGTTCAGTCC-3±’
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Remember All of the DNA is replicated. Only 50-90% of the DNA in our genome is transcribed into RNA Only 1-2% of the genome is expressed into protein coding RNA Therefore the majority of RNA expressed from our genome is non-coding RNAs
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Eukaryotic’RNA’Processing’ (Introns’are’spliced’out)
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The’Gene’for’Dystrophin’is’the’Largest’in’the’ Human’Genome’ Gene = 2,500,000 bases (2.5 Mb) + promoter Primary transcript = pre-mRNA = 2.5 Mb Mature transcript = mRNA = 14,000 bases (14 Kb) Total DNA in introns = 2,486,000 bases (2.486 Mb) Mutations result in muscular dystrophy
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Requirements for intron splicing 5 ` ’donor’site’–’typically’GU’ 3 ` ’acceptor’site’–’typically’AG’ Branch’point’sequence.’
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Splicing: How it works
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Intron Splicing: Lariat is an important intermediate structure
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http://bcs.whfreeman.com/thelifewire/content/chp14/1402001.html
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http://bcs.whfreeman.com/thelifewire/content/chp14/1402001.html
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How does the splicesome know where to go? http://bcs.whfreeman.com/thelifewire/content/chp14/1402001.html
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http://bcs.whfreeman.com/thelifewire/content/chp14/1402001.html
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http://bcs.whfreeman.com/thelifewire/content/chp14/1402001.html
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http://bcs.whfreeman.com/thelifewire/content/chp14/1402001.html
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Eukaryotic Gene Regulation 1. Controls § How much § When – time during development § Where – tissue/cell type 2. Levels § RNA v At transcription initiation – most common v During splicing or processing v Post-transcriptional stability – common- miRNA-mediated § Protein Translation initiation/elongation protein stability –ubiquitin system protein modifcation 19
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snRNA: Small Nuclear RNAs Introns Removed during pre-mRNA maturation through two transesterifcation reactions.
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