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)

http://www.sbs.utexas.edu/genetics/

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 2002,14:336-342

„RNA processing and human disease” A.V.Philips, T.A. CooperCMLS 57 (2000) 235-249

snRNP

„Pre-mRNA splicing in the new millenium” M.L. Hastings, A.R. KrainerCOCB 2001. 13: 302-309

Lubert Stryer – „Biochemistry”

„mRNA FACTORY”

„GenesVIII” B. Lewin

„Mechanisms of fidelity in pre-mRNA splicing” Robin ReedCurrent 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?

THANK YOU FOR NOT SNORING

...VERY LOUDLY