L’Splicing de les molècules d’ARN és el procés pel qual les seqüències interposades (“introns”) s’eliminen, i les seqüències restants es concatenen per a formar l’ARN madur. La investigació recent mostra que gairebé tots els gens amb splicing es veuen afectats per splicing alternatiu. Aquí, en primer lloc definim la longitud mínima d’un oligomer d’ARN per a funcionar com a lloc d’unió d’un factor d’splicing. A continuació, explorem la capacitat d’aquests oligomers per a predir estructures completes exó-intró. Destaquem els oligomers que són més informatius per a això, i demostrem que la mateixa precisió com en enfocaments anteriors es pot aconseguir amb menys oligomers. L’observació de que aquest enfocament és lluny de predir amb exactitud tota l’estructura exó-intró ens va portar a investigar els factors que juguen un paper en l’splicing co-transcripcional. Demostrem que els nucleosomes es col.loquen preferentment en els exons i plantegem la hipòtesi que juguen un paper en les decisions de l’splicing. A continuació, introduïm el “completed splicing index” i concluem que l’splicing co-transcripcional és molt generalitzat. A més, l’splicing co-transcripcional mostra vincles amb l’organització de la cromatina. A la llum d’aquests resultats, es van supervisar els canvis de la cromatina en exons diferencialment inclosos en dos teixits. Hem descobert una varietat de marques de les histones, però no totes, mostrant un comportament significativament diferent en els exons més inclosos i més exclosos. Las marques més destacades que apareixen són H3K9ac i dos estats de metilació de lisina 4. / Splicing of RNA molecules is the process, by which intervening sequences (“introns”) in the primary transcript are excised, and the remaining sequences (“exons”) are concatenated to form the mature RNA. Recent evidence shows that almost all spliced genes are affected by alternative splicing. Here, we define the minimal length of RNA oligomers that can sensibly be called splicing factor binding sites. Then, we explore the capacity of these oligomers to predict complete exon-intron structures. We highlight those oligomers that are most informative for this and show, that equal accuracy as in previous approaches can be achieved with less RNA oligomers. The observation, that this approach falls short of accurately predicting the entire exon-intron structure, led us to investigate determinants linked to co-transcriptional splicing. We show that nucleosomes are preferentially positioned on exons and hypothesize that they play a role in splicing decisions. We then introduce the “completed splicing index” and conclude that co-transcriptional splicing is very wide-spread in humans. Furthermore co-transcriptional splicing exhibits links to chromatin organization. In the light of these results, we go on to monitor chromatin changes on differentially included exons in pair-wise tissue comparisons. We find a variety of histone marks, but not all, showing significantly different behavior on up- and downregulated exons. The most prominently appearing marks are H3K9ac and two lysine 4 methylation states.

Thesis (Ph. D.)--University of Oregon, 2007. / Typescript. Includes vita and abstract. Includes bibliographical references (leaves 67-80). Also available for download via the World Wide Web; free to University of Oregon users.

Diss. (sammanfattning) Stockholm : Univ., 2004. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 5 uppsatser.

Thesis (Ph. D.)--Michigan State University. Dept. of Microbiology and Molecular Genetics, 2006. / Title from PDF t.p. (viewed on Nov. 20, 2008) Includes bibliographical references. Also issued in print.

Thesis (Ph. D.)--University of Oregon, 2007. / Typescript. Includes vita and abstract. Includes bibliographical references (leaves 76-84). Also available online in ProQuest, free to University of Oregon users.

Dissertation (Ph.D.) -- University of Texas Southwestern Medical Center at Dallas, 2007. / Vita. Bibliography: p.164-178.

Thesis (Ph. D.)--University of Texas at Austin, 2008. / Vita. Includes bibliographical references.

Thesis (Ph. D.)--University of Hong Kong, 2000. / Includes bibliographical references (leaves 193-206).

Thesis (Ph. D.)--University of Texas at Austin, 2000. / Vita. Includes bibliographical references (leaves 102-109). Available also in a digital version from Dissertation Abstracts.