ALTERNATIVE SPLICING OF mRNA. MECHANISMS ROLE IN GENE EXPRESION CONSEQUENCES by Michał Mlącki.

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Presentation transcript:

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)

GENE

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...

SPLICING

T. A. Brown – „Genomes”

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... „GenesVIII” B. Lewin „The mRNA assembly line: transcription and processing mechines in the same factory” D. Bentley COCB 2002,14:

„RNA processing and human disease” A.V.Philips, T.A. Cooper CMLS 57 (2000)

snRNP „Pre-mRNA splicing in the new millenium” M.L. Hastings, A.R. Krainer COCB :

Lubert Stryer – „Biochemistry”

„mRNA FACTORY” „GenesVIII” B. Lewin

„Mechanisms of fidelity in pre-mRNA splicing” Robin Reed Current Opinion in Cell Biology 2000, 12:

„The mRNA assembly line: transcription and processing mechines in the same factory” D. Bentley COCB 2002,14:

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?

THANK YOU FOR NOT SNORING...VERY LOUDLY