Alternativ splicing av pre-mRNA ger upphov till proteindiversitet. Histonmodifieringar kopplas till den alternativa splicingens reglering genom adaptorsystem som overfor den epigenetiska informationen direkt till splicingfaktorerna. De cis- agerande RNA- elementen pa exoner och introner med tillhorande trans- reglerande splicingfaktorer paverkas darfor direkt av specifika histonmodifieringar. En sammankopplande integrerad modell over en rad DNA- baserade processer foreslas. Denna komplexa modell ger en bild av interaktioner och paverkan mellan dessa delar. Kromatin remodellering kravs for bildandet av eukromatin. Nukleosomers placering vid exonrika regioner med specifika modifieringsmonster pekar ut exonerna samt mojliggor inbindning av RNA polymeras II som med sin CTD doman rekryterar bade splicing- och modifieringsfaktorer. Transkriptionshastigheten paverkas av nukleosomplaceringen vilket i sin tur paverkar rekrytering av spliceosomens komponenter, andra trans- agerande regulatorer och aven pre-mRNA sekvensens sekundarstruktur. Kromatin- adaptorkomplex laser av specifika histonmodifieringar och overfor informationen till splicingapparaten. Detta skapar mojlighet till den viktiga cell- och vavnadsspecifika alternativa splicingens reglering. I den integrerade modellen blir komplexiteten tydligare dar alla dessa processer interagerar med varandra och de cis- regulatoriska sekvenserna pa premRNA transkriptet. / Alternative splicing of pre-mRNA generates protein diversity. Histone modifications are connected to the regulation of alternative splicing through adaptor systems that transfers the epigenetic information directly to the splicing factors. The cis- acting RNA elements on the exons and introns together with the trans- regulating splicing factors are therefore directly affected of specific histone modifications. An integrated model over several DNA process mechanisms is suggested. This complex model explains the interactions of the different parts and how they affect each other. Chromatin remodelers are required to obtain euchromatin. Nucleosome positioning at exon rich regions with a specific modification pattern point out where the exons are, and this enable the RNA polymerase II to find and bind to the DNA. It’s CTD domain recruits both splicing- and modifications factors. The transcription rate is also affected of the nucleosome positioning and that in turn affects the recruitment of the components of the spliceosomen, other trans- acting regulators and even the formation of the secondary structure of the pre-mRNA transcript. Chromatin- adaptor complex reads specific histone modifications and transfers this information to the splicing apparatus. All this creates the possibility to regulate important cell- and tissue specific alternative splicing patterns. The integrated model makes the complex processes more clearer when all these integrates with each other and the cis- acting regulating elements on the pre-mRNA transcript.
| Identifer | oai:union.ndltd.org:UPSALLA1/oai:DiVA.org:liu-69679 |
| Date | January 2011 |
| Creators | Berggren, Jenny |
| Publisher | Linköpings universitet, Institutionen för fysik, kemi och biologi |
| Source Sets | DiVA Archive at Upsalla University |
| Language | Swedish |
| Detected Language | English |
| Type | Student thesis, info:eu-repo/semantics/bachelorThesis, text |
| Format | application/pdf |
| Rights | info:eu-repo/semantics/openAccess |
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