ALTERNATIVE SPLICING OF mRNA.

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ALTERNATIVE SPLICING OF mRNA.

• MECHANISMS
• ROLE IN GENE EXPRESION
• CONSEQUENCES

by Michal Mlacki
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PLAN OF THE PRESENTATION

• ANATOMY OF THE EUCARIOTIC GENE
• THE PROCESS OF TRANSCRIPTION
• EVENTS AFTER TRANSCRIPTION (CAPPING, SPLICING,
  POLIADENYLATION)
• ALTERNATIVE SPLICING (MECHANISMS AND CONSEQUENCES
  OF PATTERN CHANGING)

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http//www.sbs.utexas.edu/genetics/
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GENE
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TYPES OF RNA POLYMERASES

• POL I 5,8S , 18S , 28S rRNA GENES
• POL II ALL GENES ENCODING PROTEINS
• snoRNA GENES
• POL III tRNA GENES
• 5S rRNA GENES
• SOME snRNA GENES
• AND OTHER SMALL RNA GENES.

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• CAPPING
• POLYADENYLATION
• EDITING...

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SPLICING
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T. A. Brown Genomes
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PRE-mRNA (1)
T. A. Brown Genomes
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PRE-mRNA (2)
Andrew P. Read Human Molecular Genetics
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TYPES OF INTRONS

• GU AG INTRONS
• AU AC INTRONS

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HOW THE SPLICING STARTS?
Andrew P. Read Human Molecular Genetics
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CO-TRANSCRIPTIONAL EVENTS...
The mRNA assembly line transcription and
processing mechines in the same factory D.
Bentley COCB 2002,14336-342
GenesVIII B. Lewin
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RNA processing and human disease A.V.Philips,
T.A. Cooper CMLS 57 (2000) 235-249
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snRNP
Pre-mRNA splicing in the new millenium M.L.
Hastings, A.R. Krainer COCB 2001. 13 302-309
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Lubert Stryer Biochemistry
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mRNA FACTORY
GenesVIII B. Lewin
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Mechanisms of fidelity in pre-mRNA splicing
Robin Reed Current Opinion in Cell Biology 2000,
12340-345
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The mRNA assembly line transcription and
processing mechines in the same factory D.
Bentley COCB 2002,14336-342
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CONSTITUTIVE AND ALTERNATIVE
T. A. Brown Genomes
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MECHANISM(S)?

• ONE EXON ONE PROTAIN DOMAIN RULE

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WHY?

• ONE EXON ONE DOMAIN
• (EXCHANGES OF THESE DOMAINS BETWEEN PROTEINS
  IN THE EVOLUTION)

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CONSEQUENCES (1)(GOOD SIDE)

• DIFFRENT PATTERN OF SPICING
• IN DIFFRENT TISSUES
• IN DIFFRENT STAGES OF
• DEVELOPMENT
• SOME OTHER (e.g. SEX DETERMINATION IN
  DROSOPHILA)

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CONSEQUENCES (2)(BAD SIDE)

• MUTATIONS IN SEQUENCES INVOLVED IN REMOVING OF
  INTRONS MAY CAUSE UNPHYSIOLOGICAL SPLICING AND
  THEREFORE DISEASES
• MAINLY NEURODEGENERATIVE DISEASES (MYOTROIC
  DYSTROPHY,SPIRAL MUSCULAR ATROPY ETC.)

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QUESTIONS FOR THE FUTUR

• WHY THE ALTERNATIVE SPLICING SOMETIMES IS
  PHISIOLOGICAL AND SOMETIMES CAUSES DISEASES?
• HOW TO FIGHT THEM?
• HOW CAN WE USE THIS PROCESS IN GENETIC AND
  BIOCHEMICAL MANIPULATIONS?

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THANK YOU FOR NOT SNORING ...VERY LOUDLY