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ALTERNATIVE SPLICING OF mRNA. MECHANISMS ROLE IN GENE EXPRESION CONSEQUENCES. by Michał Mlącki. PLAN OF THE PRESENTATION :. ANATOMY OF THE EUCARIOTIC GENE; THE PROCESS OF TRANSCRIPTION; EVENTS AFTER TRANSCRIPTION (CAPPING, SPLICING , POLIADENYLATION);
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ALTERNATIVE SPLICING OF mRNA. MECHANISMS ROLE IN GENE EXPRESION CONSEQUENCES by Michał Mlącki
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)
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.
CAPPING… • POLYADENYLATION… • EDITING...
PRE-mRNA (1) T. A. Brown – „Genomes”
PRE-mRNA (2) Andrew P. Read – „Human Molecular Genetics”
TYPES OF INTRONS • ‘GU – AG’ INTRONS; • ‘AU – AC’ INTRONS;
HOW THE SPLICING STARTS? Andrew P. Read – „Human Molecular Genetics”
CO-TRANSCRIPTIONAL EVENTS... „The mRNA assembly line: transcription and processing mechines in the same factory” D. Bentley COCB 2002,14:336-342 „GenesVIII” B. Lewin
„RNA processing and human disease” A.V.Philips, T.A. Cooper CMLS 57 (2000) 235-249
snRNP „Pre-mRNA splicing in the new millenium” M.L. Hastings, A.R. Krainer COCB 2001. 13: 302-309
„mRNA FACTORY” „GenesVIII” B. Lewin
„Mechanisms of fidelity in pre-mRNA splicing” Robin Reed Current Opinion in Cell Biology 2000, 12:340-345
„The mRNA assembly line: transcription and processing mechines in the same factory” D. Bentley COCB 2002,14:336-342
? 5’ 3’ 5’ 3’
CONSTITUTIVE AND ALTERNATIVE T. A. Brown – „Genomes”
MECHANISM(S)? „ONE EXON = ONE PROTAIN DOMAIN” RULE
WHY? • ONE EXON = ONE DOMAIN (EXCHANGES OF THESE DOMAINS BETWEEN PROTEINS IN THE EVOLUTION)
CONSEQUENCES (1)(GOOD SIDE) DIFFRENT PATTERN OF SPICING: • IN DIFFRENT TISSUES; • IN DIFFRENT STAGES OF DEVELOPMENT; • SOME OTHER (e.g. : SEX DETERMINATION IN DROSOPHILA)
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.)
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?